Device for controlling the insertion of a needle into the skin

Abstract

An electrochemical sensor device for introducing a needle electrode into the skin of a subject to contact a biological fluid or tissue in the subject and detect a target analyte. The device has a movable part for biasing the needle electrode into the skin of the subject and means for controlling the movement of the needle electrode. After activation of the sensor device, the needle electrode is biased into the skin instantaneously and irreversibly.

Description

Technical Field

[0001] The present invention generally relates to an apparatus that is useful for introducing a needle into a subject's skin in a controlled manner and further for holding the needle in place. 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 may 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 have been used to deliver pharmacologically active substances 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 having encapsulated active substances, which slowly release the active substance into the skin over time. Hollow microneedles may be used to deliver a liquid drug composition to the skin via the needle lumen.

[0005] Sampling of interstitial fluid for subsequent analysis may also be achieved by drawing fluid from the body through the needle lumen.

[0006] In other applications, the microneedles may function as electrodes in an electrochemical sensor. The microneedles are biased into the skin to contact a biological fluid (such as interstitial fluid), and the sensor detects the presence of a target analyte in the fluid. In one type of sensor, the conductive microneedles are coated with a redox-modified aptamer to detect a specific analyte. One or more additional microneedles may be incorporated into the sensor to provide a counter electrode or a reference electrode.

[0007] The microneedles may be provided in the form of a device configured to be manually actuated by a subject in a non-clinical environment such as the home. The microneedles are brought into contact with the skin surface and then must be biased through the surface so that the microneedles extend into a layer located beneath the skin. A problem in the art is that users lack confidence in using the microneedle device and as a result may not fully embed the microneedles into the skin. Thus, the user may not be able to fully push the microneedles into the skin, thereby not being able to contact deeper tissues. Moreover, the partially embedded microneedles may be more easily removed. Damage to the skin may occur where the microneedles are dragged across the surface after removal.

[0008] To assist with application, a system may be used that includes a main device configured to contact the skin and a separate applicator device that is removed after the main device has been applied to the skin. These systems are difficult to use and are furthermore expensive to manufacture.

[0009] A further problem is that if the microneedles are not properly embedded in the skin in the first instance, the subject may be uncertain. It can be difficult, if not impossible, for the subject to look at the surface of the skin and confirm proper microneedle embedding. In case of doubt, the device is removed and a new device is applied to the skin. If the microneedles are actually properly embedded, replacement of the device is wasted.

[0010] Another problem with microneedle devices is that they are generally conspicuous and can thus be easily recognized by the subject and others. The device can catch on clothing or any other nearby object, leading to complete or partial removal. These devices may need to be worn overnight, causing significant discomfort where the subject rolls over the device.

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

[0012] One aspect of the present invention is to provide an improved needle applicator device. The improvements can be any one or more of ease of use, the possibility of proper microneedle embedding, reduction of complexity, simpler manufacturing, and lower manufacturing costs. The improvements may be provided by only one embodiment of the present invention. In some situations, the present invention may not provide any improvements and instead provide only a useful alternative to prior art devices and methods.

[0013] Discussions of documents, acts, materials, devices, articles, etc. are included in this specification 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 as they existed prior to the priority date of each claim of this application, or were common general knowledge in the field related to the present invention. SUMMARY OF THE INVENTION

[0014] Although not necessarily in the broadest aspect, in a first aspect, the present invention provides an apparatus for contacting one or more protrusions with the skin of a subject over a long period of time, the apparatus comprising one or more protrusions, each protrusion penetrating the skin; a skin contact portion defining a skin contact surface and one or more spaces that allow 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 proud of the skin contacting surface. The apparatus is configured to maintain the one or more protrusions in a first state in which they cannot contact the skin of the subject until the apparatus is actuated by the user, and the actuation causes the one or more protrusions to transition to a second state in which they are fully embedded in the skin, or enables the one or more protrusions to transition to a second state in which they are fully embedded in the skin, and the apparatus is further configured to (i) inhibit or prevent the transition of the one or more protrusions towards the first state after actuation, or (ii) require an intentional act by the user or another user to move the one or more protrusions towards the first state after actuation.

[0015] In one embodiment of the first aspect, the apparatus includes a holding portion configured to hold the skin contact surface in contact with the skin during use.

[0016] In one embodiment of the first aspect, the movable part is configured to move from the first position to the second position in a non-linear path.

[0017] In one embodiment of the first aspect, the non-linear path is generally an arcuate path.

[0018] In one embodiment of the first aspect, the movable part has a connection end and a free end.

[0019] In one embodiment of the first aspect, the free end moves a longer distance than the connection end.

[0020] In one embodiment of the first aspect, the non-linear path is drawn with reference to the free end.

[0021] In one embodiment of the first aspect, the non-linear path is less than about 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, or 3 mm.

[0022] In one embodiment of the first aspect, the degree of the arc is less than about 45°, 40°, 35°, 30°, 25°, 20°, 15°, 14°, 13°, 12°, 11°, 10°, 9°, 8°, 7°, 6°, or 5°.

[0023] In one embodiment of the first aspect, the movable part has a pivoting portion, a hinging portion, a flexing portion, or an attaching portion.

[0024] In one embodiment of the first aspect, the movable part is associated with an attaching portion.

[0025] In one embodiment of the first aspect, during use, the attaching portion is stationary and the movable part is movable relative to the attaching portion.

[0026] In one embodiment of the first aspect, the attachment portion allows the movable portion to pivot, hinge, flex, or attach.

[0027] In one embodiment of the first aspect, the attachment portion is in a fixed spaced relationship with respect to the skin contact surface.

[0028] In one embodiment of the first aspect, the attachment portion is spaced less than about 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, or 2 mm from the skin contact surface.

[0029] In one embodiment of the first aspect, the attachment portion is generally transverse to the movable portion.

[0030] In one embodiment of the first aspect, the device further includes a user-actuable release portion configured to hold the movable portion in a first position until user actuation of the release portion, and upon user actuation, the movable portion is released and enabled to move to a second position.

[0031] 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.

[0032] 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 derived internally and / or externally to the device.

[0033] In one embodiment of the first aspect, the motive force internal to the device is derived from a spring, an elastically deformable member, a shape memory member, or other biasing means, and the motive force external to the device is derived from the user.

[0034] In one embodiment of the first aspect, the device does not have an internal motive force generator configured to move the movable part from the first position to the second position.

[0035] In one embodiment of the first aspect, the holding part 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.

[0036] In one embodiment of the first aspect, the dermatologically acceptable composition is an adhesive or a functional equivalent thereof.

[0037] In one embodiment of the first aspect, the holding part is configured to mechanically hold the skin contact surface in contact with the skin.

[0038] 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 tie, a clasp, a sleeve, a stocking, a sock, a glove, a cap without a brim, a hat with a brim, an undershirt, a singlet, a shirt, a bra, a top, trousers, a scarf, a ring, spectacles, and a choker.

[0039] In one embodiment of the first aspect, one or more protruding parts are mechanically connected directly or indirectly to the movable part.

[0040] In one embodiment of the first aspect, one or more protruding parts are a wire, a needle, and / or a microneedle.

[0041] In one embodiment of the first aspect, one or more protruding parts form an array.

[0042] In one embodiment of the first aspect, the one or more protruding portions are of a sufficient length to be capable of contacting the epidermis, dermis, or hypodermis of a subject.

[0043] In one embodiment of the first aspect, the one or more protruding portions are configured 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 a sensing substance into the skin during use.

[0044] In one embodiment of the first aspect, the one or more protruding portions are each conductive, and the device further includes a circuit having an audible, visual, or tactile indicator, the circuit being configured to activate the indicator when the one or more protruding portions contact a conductive fluid naturally present on the skin.

[0045] 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 contact a conductive fluid naturally present on the skin so as to activate the indicator.

[0046] In one embodiment of the first aspect, the circuit includes one protruding portion and at least one conductive pad disposed relative to the skin, the circuit being 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.

[0047] In one embodiment of the first aspect, the device includes a housing, and when the device is applied to the skin, the movable part is in the second position, and any part of each protruding part that rises from the skin contact surface is embedded in the skin, most or substantially all parts of the housing are 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.

[0048] In one embodiment of the first aspect, the long term 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.

[0049] In one embodiment of the first aspect, the device is configured such that one or more protruding parts are non-detachable from the device or not detachable from the device without the assistance of a tool.

[0050] In one embodiment of the first aspect, the movable part and the mounting part are integral.

[0051] In one embodiment of the first aspect, the integral movable part and mounting part are made of an elastically deformable material.

[0052] In one embodiment of the first aspect, the integral movable part and mounting part are part of the circuit board of the device.

[0053] In one embodiment of the first aspect, the movable part is biased towards the second position and is maintained in the first position against the bias by a user-operable release part until the release part is actuated. When the release part is actuated, the movable part is released and enabled to move to the second position.

[0054] In one embodiment of the first aspect, the user-actuable release portion is a ledge (shelf portion) 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.

[0055] In one embodiment of the first aspect, the movable portion is in a hinge-connected relationship with the skin contact portion.

[0056] In one embodiment of the first aspect, the hinge is disposed in or towards the peripheral region of the movable portion and the skin contact portion.

[0057] In one embodiment of the first aspect, the release portion includes a member configured to maintain the movable portion in the first position, but is removable or deformable by the user so as to enable the movable portion to move to the second position.

[0058] In one embodiment of the first aspect, the member is removable by sliding it substantially across the skin contact portion

[0059] In one embodiment of the first aspect, the member is generally wedge-shaped, the device includes a hinge associating the movable portion with the skin contact portion, 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.

[0060] 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.

[0061] In one embodiment of the first aspect, the device is configured such that the transition of one or more protruding portions from the first state to the second state can be achieved by a single actuation performed by the user on the device components or by the movement of the device components in a single direction by the user.

[0062] In one embodiment of the first aspect, the single actuation or the movement in a single direction is selected from pushing, pulling, depressing, compressing, rotating, twisting, bending, squeezing, stretching, separating, breaking, joining, turning, re-orientating, hitting, tapping, and shaking.

[0063] In one embodiment of the first aspect, the device is configured such that once the transition is initiated, (i) it is not reversible by the user, or (ii) it requires an intentional act by the user or another user.

[0064] In one embodiment of the first aspect, the device is configured such that the transition is completed in about 1 second, 900 milliseconds, 800 milliseconds, 700 milliseconds, 600 milliseconds, 500 milliseconds, 400 milliseconds, 300 milliseconds, 200 milliseconds, 100 milliseconds, 90 milliseconds, 80 milliseconds, 70 milliseconds, 60 milliseconds, 50 milliseconds, 40 milliseconds, 30 milliseconds, 20 milliseconds, 10 milliseconds, 9 milliseconds, 8 milliseconds, 7 milliseconds, 6 milliseconds, 5 milliseconds, 4 milliseconds, 3 milliseconds, 2 milliseconds, or less than 1 millisecond.

[0065] In one embodiment of the first aspect, the device is configured such that the transition is substantially instantaneous.

[0066] In one embodiment of the first aspect, the device is configured such that the start or completion of the transition is associated with a tactile, auditory, or visual feedback signal to the user.

[0067] In one embodiment of the first aspect, one or more protruding portions extend from the body, and the body receives an action during the transition.

[0068] In one embodiment of the first aspect, the transition includes the movement of one or more protruding portions from a first position to a second position.

[0069] In one embodiment of the first aspect, the device includes a snap mechanism that prevents the movement of one or more protruding portions from the first position until a user applies at least a threshold level of force to a component of the device by an actuation action. Once at least the threshold level of force is applied, the one or more protruding portions are caused to transition to the second position or are enabled to transition to the second position in about 100 milliseconds, 90 milliseconds, 80 milliseconds, 70 milliseconds, 60 milliseconds, 50 milliseconds, 40 milliseconds, 30 milliseconds, 20 milliseconds, 10 milliseconds, 9 milliseconds, 8 milliseconds, 7 milliseconds, 6 milliseconds, 5 milliseconds, 4 milliseconds, 3 milliseconds, 2 milliseconds, or less than 1 millisecond, or substantially instantaneously.

[0070] In one embodiment of the first aspect, the snap mechanism includes an elastically deformable formation that must be deformed to enable one or more protruding portions to move from the first position to the second position.

[0071] In one embodiment of the first aspect, the elastically deformable formation is associated with one or more protruding portions or another component of the device

[0072] In one embodiment of the first aspect, the another component is a component that remains stationary during operation.

[0073] In one embodiment of the first aspect, the another component is the housing of the device, a component of the device that contacts the skin of the subject to which the device is applied, or a component of the device through which one or more protruding portions extend.

[0074] In one embodiment of the first aspect, after the operation of the device, the snap mechanism locks one or more protruding portions in a second position.

[0075] In one embodiment of the first aspect, the device includes a main body, one or more protruding portions extend from the main body, and the snap mechanism includes a portion extending from the main body.

[0076] In one embodiment of the first aspect, the device includes biasing means configured to maintain one or more protruding portions in a first position until an operation occurs, or to rapidly move one or more protruding portions from the first position to a second position, or to maintain one or more protruding portions in the second position after the operation has occurred.

[0077] In one embodiment of the first aspect, the device includes one or more catches, and the one or more catches are configured to allow movement of one or more protruding portions from a first position to a second position while preventing movement of one or more protruding portions back towards the first position.

[0078] In a second aspect, the present invention provides a method of contacting a protrusion with the skin of a subject, the method comprising providing a device according to any embodiment of the first aspect, contacting the skin contact surface of the device with the skin, and moving a movable portion from a first position to a 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.

[0079] In one embodiment of the second aspect, 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. BRIEF DESCRIPTION OF THE DRAWINGS

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DETAILED DESCRIPTION OF THE INVENTION

[0103] Unless otherwise indicated herein, the components of the drawings labeled with the same numerals are considered to be the same components or at least functionally similar components when used across different drawings.

[0104] The drawings are not drawn to any specific scale or dimension and are not presented as a perfectly accurate representation of various embodiments.

[0105] 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 only and not by way of 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.

[0106] 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.

[0107] References to "one embodiment" or "an embodiment" throughout this specification mean that a particular configuration, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, although they may.

[0108] As used herein, positional terms such as "lateral", "across", "above", "over", "below", "higher", "lower", "upward", "downward", "plan view", etc. are to be considered with reference to the device of the present invention when applied to an area of the subject's skin facing upward, such as the upper surface of the subject's thigh when a person is sitting on a chair. The device can be applied to skin regions having different orientations relative to the defined upright direction, in which case one of ordinary skill in the art can adequately reconfigure the aforementioned positional terms.

[0109] The term "subject" is used to refer to an animal (including humans and non-human animals) to which the present device may be applied. The term "user" is used to refer to a human who applies the device 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.

[0110] Unless the contrary intention is apparent from the context of use, "needle", "microneedle", and "wire" are used interchangeably. Each is functionally identical or similar and can be inserted into the subject's skin to contact a biological fluid.

[0111] "Biological fluid" may be any biological fluid of a subject, including, but not limited to, interstitial fluid (ISF), blood, saliva, tears, milk secretions, nasal secretions, tracheal secretions, bronchial secretions, alveolar secretions, gastric secretions, gastric contents, glandular secretions, vaginal secretions, uterine secretions, prostate secretions, semen, urine, sweat, cerebrospinal fluid, glomerular filtrate, liver secretions, bile, or exudates, any of which are contacted in vivo with the needle electrode of an electrochemical sensor during use. "Tissue" includes a volume containing one or more cells.

[0112] Various distinct embodiments of the present invention are disclosed herein (whether by way of the drawings or the description), and the embodiments have one or more of the configurations disclosed in the context of this specification. It will be apparent that there is no intention to limit the application of a particular configuration or combination of configurations to its use in the embodiments in which it is disclosed. 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.

[0113] However, it will be apparent to those skilled in the art that certain combinations may be less preferred or are actually contraindicated. For example, if configuration A is required for configuration B to operate, an embodiment including the combination of configurations B, C, and D may be inoperable.

[0114] The present invention is based, at least in part, on the discovery that an improved or alternative device for inserting a needle into the skin of a subject includes a movable portion that biases a microneedle against the skin of the subject in a controlled manner. The manner of control is more fully described below.

[0115] The movable part may move in a non-linear path. Moreover, the non-linear path may be of a limited length, in which case the path is arcuate with a limited degree measure. With this configuration, the main movable part of the device only requires a limited range of motion (range of movement) in the vertical direction to insert the microneedle into the subject's skin in contact with 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.

[0116] 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 or 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.

[0117] Certain embodiments of the present invention have additional configurations that provide further advantages or useful alternatives over the prior art when used alone or in combination with other configurations. Such embodiments are more fully described by reference to the non-limiting preferred embodiments described below.

[0118] Referring to FIG. 1, a basic form of the device (10) having a microneedle array (one microneedle is marked 15) attached to the movable part is shown, and the movable part is, in this embodiment, an elastically deformable arm (20). The arm (20) is biased to take a linear configuration (20b), but is initially presented to the user in a curved and bent upward state as shown in the dashed line representation (20a).

[0119] The device (10) includes a rigid housing (25) having a skin contact portion (30) on its lower side that defines a downward-facing skin contact surface (35). The skin contact surface (35) is placed on the skin of the subject and is held therein by an area 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, doing housework, brushing over an object while walking, and mild to moderate intensity sports activities. The level of the adhesives is typically not so great as to cause any difficulty, discomfort, pain, irritation, or skin damage when removing the device.

[0120] Exemplary adhesives are synthetic rubber adhesives or pressure-sensitive acrylic adhesives of the type used for medical tapes. 3M TM A double-sided medical tape such as 3M 1577 tape may be used, with one side adhering to the device and the other side adhering to the skin of the subject.

[0121] The skin contact portion (30) includes a space (45), the margins of which are marked at (45a) and (45b). The space (45) provides respective passages through which the microneedles (15) pass, enabling the distal regions of the microneedles to penetrate and be embedded in the underlying skin (50) when the arm (20) is in the straight position (20b).

[0122] The arm (20) is held in its flexed state by a ledge (shelf portion) (55) that functions as a release means. When the user desires to insert the microneedle (15) into the skin (50), the user depresses the button (60) as indicated by the arrow. The lower surface of the button (60) presses against the ledge (55), and the ledge (55), which is formed from a rubbery material or, for example, from flexible protrusions on the inner surface of the housing (10) and has some ability to deform, bends downward under a force that releases 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 microneedle (15) into the skin (50) located below. The ledge (55) is configured to exhibit sufficient elasticity to resist the biasing force within the arm (20a), but the resilience is not sufficient to resist the downward force applied by the button (55) when depressed.

[0123] 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 subject's skin (50). As will be understood, any movement of the arm (20) away from the position (20b) may pull the microneedle (15) out of the skin (50). Considering the bias of the arm (20) towards the position (20b), a locking mechanism to maintain the arm in the position (20b) may not be necessary. However, if required, a suitable locking mechanism is described below for the embodiment of FIG. 2A.

[0124] Figure 2A shows an alternative basic form of the device (200) such that the arm (205) is rigid and is hinge-connected to the housing (25) via a hinge pin (210). The embodiment of Figure 2A operates in the same manner as the embodiment of Figure 1 as long as the ledge (55) acts as the release means. However, in the embodiment of Figure 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) to bend the ledge (55), thereby releasing the free end of the arm (205a). The button (215) continues to be pressed down 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).

[0125] It will be understood that the hinge-connected configuration of Figure 2A does not resist the arm (205) from hinge-actuating away from the position (205b) while the device is worn. Thus, there is a risk that the microneedle (15) may be pulled out of the skin (50) while in place. Accordingly, a locking mechanism is provided (205b) to maintain the arm in a predetermined position. The locking mechanism includes a deformable latch (220) that is manufactured, 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, after contact with the rigid arm (205), the entire latch (220) is pressed to bend leftward (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) resumes its normal upright position (as shown), and the free end of the arm (205b) seats firmly in a recess in the base of the latch (220).

[0126] 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 a release means (55), which is removable by the user in this embodiment 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 so as to assume a second position (205b).

[0127] It will be noted in the embodiments of FIGS. 1, 2A and 2B that when released from the ledge (55), the free end of the arm (20 or 205) moves in a non-linear manner 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, although in some embodiments it is a segment of a circle (see, for example, the embodiment of FIG. 2A).

[0128] 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 fact, in these embodiments (and certain other embodiments), the device is intentionally configured such that the arm cannot move along any path outside the path between the first and second positions. Stated another way, the device may be configured such that the arm cannot move along any path outside the shortest distance between the first and second positions.

[0129] By providing a restriction on the path along which the arm moves, advantages are provided as long as the height of the device (in the vertical direction as shown) is also restricted. Thus, the device may take a low profile that extends a relatively short distance above the subject's skin (in the sense of dimensions).

[0130] Next, referring to FIGS. 3A and 3B, a preferred device is shown that is generally configured in accordance with and operable in general agreement with the embodiment of FIG. 1. The arm (20) is formed integrally with a PCB (65) that carries various electronic components required for the operation of the device. The PCB material is elastically deformable such that the arm (having the microneedles attached to its end) bends upward as shown to position the arm in a first position, but when released, due to the natural bias within the arm towards a second position, it is able to assume the second position.

[0131] The arm (20) is maintained in the first position by the end of the arm (20) being positioned on the ledge (55), as most clearly shown in FIG. 1A. In this position, the microneedle (15) is held within the device and there is no portion that extends through the space (45). This is the configuration in which the device is provided for use and in which the device is applied to the subject's skin.

[0132] The arm (20) has a micro-needle mounting block (70) connected to the arm that supports the micro-needles. The mounting block (70) also includes conduits (not shown) that conduct current from each of the micro-needles (15) to one of a number of connection points (75) on the PCB (65). With this configuration, electrical signals may be transmitted to and / or from the micro-needles embedded in the subject's skin. For example, the device may be configured as a sensor having micro-needles configured to contact a biological fluid within the subject's body and detect an analyte therein. The biological fluid may be, but is not limited to, interstitial fluid, blood, or a mixture thereof. Electrical signals from the micro-needles are conveyed to the PCB for amplification, filtering, encoding, analysis, transmission, or any other electrical or electronic process.

[0133] In this embodiment, the PCB serves a dual function of holding the electronics of the device and also functioning as motive means for moving the micro-needles from an internal position of the device to an external position. The PCB material has been found to be suitable for providing a limited range of motion that is preferred for the arm of the present device. This configuration reduces the number of components within the device.

[0134] The upper surface of the housing (25) shows the actuating surface of a button (215) that can be depressed by the user's finger. The button (215) is biased upwardly (as shown) by a spring or because it is integrally formed with the housing (25) material. In the latter form of biasing, the button (215) may be attached to an arm that is integral with the housing material and biased so that the upper surface of the button (215) is coplanar with the housing (25).

[0135] The lower portion (not visible to the eye) of the button (215) contacts the upper surface of the arm (20), which upper surface is the rear surface of the PCB (65) such that depression of the button (215) biases the arm (20) downwardly so that the arm moves away from the ledge (55) and assumes a second position. In the second position, it will be appreciated that the microneedles extend through their respective spaces (45) and are embedded into the underlying skin (e.g., the epidermis, dermis, or hypodermis of a subject).

[0136] 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.

[0137] 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 such that the microneedles (15) do not retract into the device and remain 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 specification.

[0138] The housing (25) includes opposing recesses (80) to facilitate gripping between the user's thumb and second finger and holding of the device against the skin surface. The user's first finger can freely actuate the button (215) to embed the microneedles (15) into the underlying skin.

[0139] The skin contact surface (35) may have a dermatologically acceptable adhesive layer (not shown) applied to the skin contact surface so as to maintain the device in place on the subject's skin over a long period of time. The adhesive layer can cover part or substantially all of the skin contact surface (35). As described for other embodiments of the devices described herein, a manually releasable flexible layer may cover the adhesive until the device is applied to the skin.

[0140] Referring now to FIGS. 4, 5A, 5B, 6, and 7, there is shown a preferred device generally configured in accordance with and operable in substantial conformity with the embodiment of FIG. 2B.

[0141] The embodiment includes an upper housing portion (25) and a skin contact portion (30). A removable flexible layer (90) is also provided that is grippable via a tab (95), the removal of which exposes a dermatologically acceptable adhesive on the skin contact surface (35). As explained 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, prevent contamination of the adhesive layer prior to use, and / or prevent premature attachment of the adhesive to packaging or other surfaces. In a particularly preferred embodiment, in addition to covering the adhesive layer, the flexible layer (90) extends over the space (45) to also help prevent contamination of the microneedles (15) and prevent unintentional needle sticks to the user.

[0142] 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 subject's biological fluid. The holding portion may be dedicated to that function or may perform another function.

[0143] In many situations, a holding portion that is a dermatologically acceptable adhesive or that includes a dermatologically acceptable adhesive would be useful. The adhesive allows for simplicity in the application of the device by the user, often only requiring removing 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.

[0144] As an alternative to the use of an adhesive, the holding portion may be some 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 keep the device firmly applied to the subject. Alternatively, the device may be incorporated into a wearable item such as a glove or a 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 with a separate wearable item (e.g., by complementary hook and loop means) or may have a wearable item integral with the device.

[0145] In some embodiments, the device is simply held by a wearable item that contacts the housing. For example, the holding portion may be a snug-fitting elasticised glove that fits over the device.

[0146] In some embodiments, the holding portion is any surface or part of the device that contacts the skin of the subject, and the configuration of the subject is at least partially involved in maintaining the device in a predetermined location on the subject. For example, the device may be configured to be held between two parts of the body in normal close juxtaposition or within an existing anatomical structure. The device may be shaped and / or dimensioned to be held between toes, between buttocks, within the groin, within the buccal cavity, within the nostrils, within the ear canal, or within the navel.

[0147] In other embodiments, the device housing may be shaped and / or dimensioned to fit snugly over, for example, a digit, toe, or ear. 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 portion (such as a finger).

[0148] Each of the foregoing embodiments is considered to be a holding part in the context of the present invention.

[0149] The device further includes a release member (100) having a gripping portion (105) and a wedge portion (110), the function of which is described more fully below.

[0150] Referring next to the exploded views of FIGS. 5A and 5B, components similar to those in the foregoing figures will immediately become apparent.

[0151] In this embodiment, the motive force that moves the arm (205) and thereby biases the microneedle (15) into the underlying skin is provided by the user. In use, the user places a finger on the upper housing 25 and presses downward. Further, the arm (205) is movable via a hinge mechanism.

[0152] 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 a hole of the lug (115). It will be apparent that the arm (205) can be hingedly connected to the skin contact portion (30) to enable movement from a first position to a second position.

[0153] The arm (205) is presented to the user having the arm in the first position. The arm (205) is maintained in the first position by the wedge portion (110) of the release member (100). Before removal of the release member (100), the wedge portion is inserted between the skin contact portion (30) and the arm (205), thereby holding the microneedles within the device.

[0154] When attempting to apply the device to the subject's skin, the user removes the flexible layer (90) by pulling on the tab (95) to 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.

[0155] Once the device is applied to the skin, the user grasps the gripping portion (105) and pulls it horizontally to the left (as shown) to completely remove the release member (100). The release member (100) no longer has any function and is discarded at this point. Removal of the release member (100) releases the arm (205) from the first position and enables it 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 microneedles (15) extend into the skin located below through the space (45).

[0156] As will be appreciated, the release member (100) may be configured such that the upper housing (25) of the device does not close against the skin contact portion (30) when not intended by the user. The release member (100) is inserted between the upper housing (25) and the skin contact portion (30), or otherwise juxtaposed, to prevent closure 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 closure also prevents movement of the arm (205) from the first position to the second position. Thus, when the release member (100) is in place, inadvertent access to the tip of the microneedle and causing microneedle contamination or damage cannot occur. When using the device, the user removes the release member (100) as a step in the use process. In a preferred embodiment of device use, the user first adheres the device to the subject's skin and then removes the release member (100) before pressing the upper housing (25) to insert the microneedle into the skin.

[0157] 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 protrusions that fit into recesses in either the upper housing (25), the skin contact portion (30), or 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 the friction between the release member (100) and 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 such that when the release member (100) is in place, it is proximate to a Hall effect sensor positioned in either the upper housing (25) or the skin contact portion (30). 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 configuration that is ready for use, or converting the electronic circuit configuration 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.

[0158] 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 downward toward 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) facing 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 at the skin contact portion (30) to cover the protruding microneedle. In another example of this embodiment, the release member (100) is flexibly attached to the device, so that the release member (100) remains attached to the device after the device is pulled out by the user, and then, after the device is removed from the subject after use, it is repositioned to cover the protruding microneedle. 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 engageable with the upper housing (25) after the release member (100) is once removed, in which case 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.

[0159] 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 may make removal of the device from the skin difficult. An example of such a configuration includes leaving a portion of the skin contact surface (35) uncovered by the adhesive such that a gap exists between the subject's skin and the surface (35), in which case the user uses the gap as a leverage point to help pull the device away from the skin by breaking the adhesive bond. In another example, a leverage mechanism that is not disposed on the skin contact surface is incorporated to allow for a higher 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, in which case the user pulls on the tab with sufficient force to stretch and yield the adhesive layer to further peel the adhesive away from the skin contact surface (35) and the skin.

[0160] 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 on at least one of the upper housing (25) and the skin contact portion (30) that is lockably engaged when the upper housing (25) is not being pushed. The configuration on at least one of the upper housing (25) and the skin contact portion (30) is distorted when the upper housing (25) is pushed down to disengage the release member (100) and allow the release member (100) to be withdrawn.

[0161] In still other embodiments, the release member (100) need not be removed from the device by the user. According to these embodiments, the release member (100) has a sufficiently high rigidity flexible element that does not substantially deflect when exposed to the closing forces that may be present on the device during manufacture, storage, and in the user's hand, before application to the subject, but is flexible enough to deflect when the user intentionally applies a closing force to the device when the release member is applied to the subject's skin. When bent in such a way, the release member (100) is deflected 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).

[0162] 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 the length of the hole 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 inserted.

[0163] 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 help hold 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 help hold the release member in place until intentional removal by the user.

[0164] 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, preventing any hinge movement of the arm (205). In the illustrated embodiment, the latch (220) can deflect in response to movement of the arm (205) towards the closed position, but returns 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.

[0165] 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 may act on the upper housing (25), which then holds the arm (205) in the second position. Further alternatively, the locking portion may act on the PCB (65), which then holds the arm (205) in the second position.

[0166] In other embodiments, the locking portion includes a recess, and a protrusion on the upper housing (25) is inserted into the recess to lock the upper housing (25) in the closed position (i.e., the arm (205) is in the second position). In one embodiment, the locking portion allows the housing (25) to close relative to the skin contact portion (30), such that once the upper housing (25) is closed, the locking portion is designed to allow the locking portion to lock the upper housing (25) in place at the closed position, and includes a flexible element designed to allow 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 allows the protrusion to move, allowing the upper housing (25) to close relative to the skin contact portion (30), and then, when the housing (25) closes relative to the skin contact portion (30), 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 that is sufficiently deformable to allow 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. In embodiments that are less preferred but still functional, the flexible element includes a coil spring.

[0167] 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 down steel, stainless steel, or other materials known in the art having suitable mechanical properties.

[0168] 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.

[0169] In a particularly preferred embodiment of the present invention, the force required to deflect or otherwise move the flexible element is designed to be large enough so that the pressure that the user needs to supply to deform the flexible element and thus close the upper housing (25) towards 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 the force is used to ensure that it is sufficient to insert the microneedles into their intended positions embedded in the skin.

[0170] In other embodiments, the locking portion includes at least one adhesive region disposed 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.

[0171] In another embodiment of the present invention, the locking portion can assume three different stable states. In the first state, before the upper housing (25) is pushed downward towards the skin contact portion (30) to close the device, the locking portion is in a disengaged configuration. In the second state, the locking portion is in the first engagement position. When the locking portion is in the first engagement position, it serves to lock the microneedle (15) in the implanted position within the skin (i.e., the arm (205) is in the second position). In the third state, the locking portion is in the second engagement position. In this state, the locking portion locks the device in the release position (i.e., the arm (205) is in the first position), and the microneedle is retracted into the device to improve the likelihood of a needle stick injury resulting from the microneedle protruding after device use. In an example of this embodiment, the locking portion includes a user engagement portion that can be gripped by the user or otherwise engaged, for example, by engaging a fingernail under a protruding ledge, so that the user can deflect the flexible portion of the locking portion. According to this example, to close the device, the user presses the upper housing (25) and locks the upper housing (25) in place, as in other embodiments disclosed herein. When it is desirable to remove the device from the subject, the user engages the locking portion to release the upper housing (25) from the skin contact portion (25), deflects the locking portion in a first direction, and then deflects the locking portion in a second direction to lock the device in the open position (i.e., the arm is in the first position), and the microneedle is in the withdrawn position. 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, towards the body of the device. When sufficiently deflected in the second direction, the locking portion is designed to engage safely within a recess, for example, to prevent unintentional closure of the device.

[0172] In some embodiments of the present invention, the downward force on the microneedle 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, the 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. The spring is distorted or compressed when the device is closed so as to apply a downward force on the microneedle when the device is in the closed position.

[0173] Although not an essential configuration of the present invention, a PCB (65) is required for many applications for the purpose of conducting current to, from, or through the skin by the microneedle. In that regard, the PCB may carry 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 comprises a power source via a button cell, of course. TM The embodiment shown in FIG. 3A further includes a light emitting diode (LED) (120) visible to the user. One function of the LED (120) is to confirm to the user and / or subject that the microneedle is properly embedded in the skin upon application and remains properly embedded over an extended period of wear.

[0174]

[0175] ​The LED is electrically connected to a PCB (65), which in turn is electrically connected to the microneedles (15). Appropriate embedding of the microneedles can be determined by referring to one or more of the current, resistance to current, or impedance between two microneedles.

[0176] Alternatively, appropriate embedding of a single microneedle can be determined by referring to one or more of the current, resistance to current, or 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 instances, the conductive pad is placed on the surface of the housing that contacts the skin. This conductive pad cooperates with at least one of the microneedles to complete an electrical circuit when the microneedle is inserted into the skin. Completion of this circuit is used to indicate correct insertion of the microneedle.

[0177] The electronics involved can be simple, any of which can be a biological fluid of the skin, such as interstitial fluid (which is inherently conductive), and acts to complete a circuit including the LED. Assume that appropriate embedding is indicated by 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 correct embedding.

[0178] To provide a higher level of assurance of correct microneedle embedding, a more sophisticated electronic configuration may be required. For example, considering whether the minimum length of the microneedle is embedded, thereby providing confirmation of the insertion of the microneedle 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 more complete embedding of the microneedle. Program instructions executed by an on-board processor or otherwise associated with the device may use a parameter such as a current flow as an input to provide an indication of the degree of microneedle embedding (optionally along with other physiological or environmental parameters).

[0179] 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 slightly above the minimum operating voltage that enables the subject to access a replacement battery (or a replacement device if the battery is not user-serviceable) before the device becomes inoperable.

[0180] In other embodiments, the LED may generate an output display of the data connection status. For example, the LED may alternately flash 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 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 may monitor the connection status of the module and cause the LED to generate an output when the connection is made and / or lost. The smartphone application software may be configured to alert 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 of warning the subject may be by the device itself.

[0181] A similar output function for the LED may be provided by a buzzer or a miniature speaker for providing audible output understandable by the subject. The output may be, for example, a tone, a series of tones, or a synthesized voice.

[0182] Now, refer to an alternative embodiment of the device shown in FIG. 8B, which is a modified version of the embodiment shown in FIGS. 4 - 8A. The embodiment of FIG. 8B includes a temperature sensor (900) that extends through a space (905) in the skin contact portion (30) during operation so as to contact the surface of the subject's skin. The temperature sensor (900) 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.

[0183] The temperature sensor may be disposed within a pocket or other formation dimensioned to receive the temperature sensor. The pocket may be made of a thin sheet-like material of plastic, such as 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 movement of thermal energy from the pocket wall to the temperature sensor.

[0184] 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 strongly against the skin surface will push blood out of the skin capillaries, thereby artificially cooling the skin surface.

[0185] 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 directs the thermal energy from the skin away from the temperature sensor along a non-specified path.

[0186] An 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.

[0187] 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 intervening material is required for the thermal energy to cross, a temperature close to the actual skin temperature is expected.

[0188] In a further modification, the temperature sensor may be an infrared sensor module, in which case at least the material of the pocket floor should not substantially interfere with its operation. A space is envisioned to 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.

[0189] The signal output from the temperature sensor (900) 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 series of stored calibration curves, each curve being performed at a given temperature. Based on the output of the temperature sensor (900), an appropriate calibration curve may be selected, and thus, a more accurate analyte concentration may be determined.

[0190] The embodiment of FIG. 8B includes a release member (100) having paired protrusions (the first protrusion is marked 310, and the second protrusion of the paired protrusions is obscured by the first protrusion). The protrusions (910) extend downward through a space (915) in the skin contact portion (30). The function of the protrusions (910) 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 protrusions (910) to exit the space (915) vertically, allowing 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 be caused to extend prematurely through the space (45), may be contaminated by contact with air or objects, or may be physically damaged, for example, by snagging on clothing.

[0191] The device may be configured with a microneedle device that controls the microneedles such that, upon application and activation by the user to the skin, the microneedles are pushed into the skin in one direction and fully embedded within the skin. The microneedles are not permitted to be partially embedded (i.e., extend less than the desired depth into the dermal tissue) nor are they permitted to be removed from the skin during the embedding process.

[0192] After the application of the microneedle device to the skin of the subject (the process typically includes exposing the adhesive surface of the device and contacting the adhesive surface with the skin), the user activates the device (e.g., by pressing a button), and according to the present invention, the microneedles are biased in one direction through the skin surface so as to be fully embedded in the underlying tissue in a single action. The device may be configured such that the user cannot pause the embedding process when the microneedles are less than fully embedded, or the device may be configured such that the user cannot reverse the embedding process to withdraw or partially withdraw the microneedles from the skin.

[0193] In some embodiments, the microneedles are locked in a fully extended state after complete embedding. Without destruction of the adhesive (or other means for holding the device on the skin), the microneedles remain fully embedded and thus are in complete contact with the dermal tissue as desired.

[0194] In some embodiments, the device may be further configured such that the embedding of the microneedles occurs rapidly, in some embodiments substantially instantaneously. In this way, the user may activate the device with the microneedles being rapidly pushed into the skin. For example, a snap mechanism may be incorporated into the device, which in some embodiments requires the user to apply a minimal amount of force to the components of the device. Once that minimal force is applied, there is a rapid transition from a first state (e.g., no microneedle embedding) to a second state (e.g., complete microneedle embedding). Advantageously, some clear positive tactile, visual, or auditory feedback is provided to the user to confirm that the device has been fully activated.

[0195] The present device may offer an advantage over the prior art in that a user can reliably embed a microneedle into the skin of a subject with confidence in a reproducible manner. Thus, the microneedle extends to a sufficient necessary depth within the dermal tissue such that the tip contacts the target volume of the interstitial fluid. The fluid may be contacted with a sensing aptamer or a drug conjugated to the microneedle, or may be withdrawn through a lumen in the microneedle for subsequent analysis.

[0196] Reference is next made to FIGS. 9-18, which show embodiments of a device in which a microneedle extends from a body (300) and the body (300) moves in a linear manner between a first position and a second position. However, it should be noted that the embodiments of FIGS. 1-8 (where the microneedle is attached to a member that moves in a non-linear manner) may be configured to include one or more of the configurations of FIGS. 9-18, and vice versa.

[0197] Referring to FIG. 9, the device functions similar to a suction cup. A flexible skirt (305) seals the surface of the body (300) and the skin (50) of the subject. The button (215) is pushed downward by the user (FIG. 9A), thereby discharging the compressed air below the skirt (305) through a one-way valve (310). When the button is fully depressed, the micro-needles of the body (300) are fully embedded in the skin (50). As understood, when the button (215) is depressed, there is some resistance to the button moving upward (and withdrawing any micro-needles from the skin) because the one-way valve (310) cannot accept the air below the skirt (305). An attempt to move the body (300) upward creates a vacuum below the skirt, and the vacuum functions to pull the body downward. Thus, the body (300) and its associated micro-needles move substantially in one direction toward the skin. In this embodiment, the device may be held on the skin for an extended period of time by a seal formed between the skirt (305) and the skin (50) and a vacuum created below the skirt (305). When the device must be removed, the user may lift the edge of the skirt (305) to break the seal formed thereunder with the skin (50).

[0198] In the embodiment of FIG. 10, a first wedge-shaped body (315) is moved laterally by the user (FIG. 10A) so as to slide over a second wedge-shaped body (320), thereby moving the second wedge-shaped body (320) downward to embed the micro-needles extending from the body (300) into the skin (FIG. 10B). The opposing surfaces of the first wedge-shaped body (315) and the second wedge-shaped body (320) may frictionally engage to some extent to resist any reverse movement of the first wedge-shaped body (315) back to its original position. In one embodiment, the opposing surfaces are formed with teeth so as to form a ratchet-like configuration, thereby essentially preventing any reverse movement of the first wedge-shaped body (315) and preventing any withdrawal therefrom when the micro-needles are fully embedded.

[0199] In the embodiment of FIG. 11, complementary inclined formations (325a, 325b) are provided on an axially rotatable knob (330) and a downwardly located body (335), respectively. When the knob (330) is rotated by a user, the downwardly located body is forced downward and thus acts on the body (300) to bias the microneedle into the underlying skin. To prevent any reversal of the rotation of the knob (330), the outer periphery of the knob (300) may have formations that engage recesses in the opposing surface of the housing (25). Thus, under the rotational force provided by the user, the formations move in and out of the recesses to allow the knob (330) to rotate in the desired direction. In the absence of any applied rotational force, the formations remain in the recesses to prevent any reverse rotation. When the knob (300) is fully rotated and the microneedle is fully embedded, the knob (300) is locked in place by the juxtaposition of respective vertical surfaces (one marked 340) on the inclined formations (325a, 325b).

[0200] To operate the embodiment of FIG. 12, the user moves the shutter (345) laterally. Initially (FIG. 12A), the shutter (345) contacts a leaf spring (350) that holds both in a compressed state. Thus, the leaf spring (350) is separated from the body (300). When the shutter (345) is slid to the right (FIG. 12B), the leaf spring (350) momentarily contacts the body (300) and is thereby allowed to extend through the shutter space to rapidly bias the body downward. The bias of the leaf spring (350) ensures that the movement of the body (300) is in one direction, i.e., downward. The function of the coil spring (355) is to maintain the shutter (345) in the outward position shown in FIG. 12A until actuation is required.

[0201] In the embodiment of FIG. 13, the body (300) is attached to the spring-loaded arm (360). Before actuation (FIG. 13A), the vertical coil spring of the spring-loaded arm (360) is compressed behind the flange (361) of the arm (360). The arm (360) is held in the contracted state shown in FIG. 13A by a horizontal plate (362) having a notch (363) that contacts the flange (361). To operate the device and deploy the micro-needle, the user displaces the notch (363), thereby releasing the arm (360) and allowing the coil spring (360) to expand, thereby causing the arm (360) to move rapidly downward (FIG. 13B) by moving the plate (362) laterally. The downward movement of the spring-loaded arm (360) rapidly biases the body exterior (300) downward so as to fully embed the micro-needle into the skin (50). After actuation, the coil spring maintains the arm in the extended position shown in FIG. 13B, thereby resisting any withdrawal of the micro-needle from the skin. The function of the horizontal coil spring (368) is to maintain the plate (362) in the outward position shown in FIG. 13A.

[0202] The embodiment of FIG. 14 includes a small bladder (370) in gas communication with a compressible valve (375). To operate the device, the user squeezes the valve (375) as shown in FIG. 14A, allowing the expelled air to pass through a one-way valve (380) and inflate the bladder (370). The inflation of the bladder then biases the body (300) and the micro-needle downward and into the skin (50) as shown in FIG. 14B. The one-way valve (380) prevents the micro-needle from moving in the reverse direction during actuation and also prevents the withdrawal of the micro-needle after actuation.

[0203] In the embodiment of FIG. 15, the body (300) is directly connected to the button (215). The helical spring (385) biases the button (215) in the upward direction to make it operable. The housing (25) has an upper annular flange (390) and a lower annular flange (400), and each flange has a tooth-shaped profile. The button (215) has an annular flange (410) with the same tooth-shaped profile as the tooth-shaped profile of the housing. Before actuation (FIG. 15A), the upward-facing horizontal plane of the flange (410) contacts the downward-facing horizontal plane of the flange (390) by the action of the spring (385). After the button (215) is depressed, the flange (410) moves downward and, with the deformation of the flange (410) (or even with the deformation of the button (215) wall located under the flange (410)), contacts the flange (400), enabling the button (215) to be fully positioned at the bottom of the housing (25) as shown in FIG. 15B. When fully positioned, the body (300) is at its lowest point and the microneedle is fully embedded in the skin (50). The lower flange (400) prevents the button (215) from moving upward and thus also prevents the microneedle from being withdrawn. The upward-facing horizontal plane of the flange (410) contacts the downward-facing horizontal flange (400), thereby preventing relative movement between the button (215) and the housing (25).

[0204] Next, referring to FIG. 16, the embodiment includes a button (215) that extends through a plate (415) and is connected to the body (300) at its end. The button has an annular flange (420) and a downwardly tapered region (425) on its shaft. The plate (415) has a vertical collar (430) extending from its upper surface, and the collar (430) has an inwardly rotated lip (435). A helical spring (440) surrounds the collar (430) and the tapered region (425) and biases the flange (420) and the plate (415) to maintain the button (215) in the upward position shown in FIG. 16A where it is operable. Depression of the button (215) by the user causes the flare region (425) to pass completely into the collar (430) as a result of deformation of the flare region and / or the lip (435). The upwardly directed surface of the tapered region (425) contacts the lip (435) and basically locks the button (215) in the position shown in FIG. 16B, preventing withdrawal of the microneedles from the skin (50).

[0205] The embodiment of FIG. 17 includes opposing spring load columns (440) that are biased to take the position shown in FIG. 17A. Note in FIG. 17A that the lower ends of the columns (440) extend beyond the lower surface of the device so that the device as a whole is suspended above the skin (50). Each column (440) has a vertical arm (445) that extends inwardly therefrom. In this embodiment, the columns (440) and the arms (445) have a weak region (450) at the intersection that is intended to bend or break when a force is applied to the columns (440), but are integrally formed. Each of the arms (445) has a pivot point (455) and at the end holds the microneedle support body (300) in a retracted position against the bias of the coil spring (460). To activate, the user presses the housing (25) downwardly, thereby biasing the columns (440) upwardly. Since the arms (445) are held at the pivot points (445), the weak portion (450) breaks and the ends of the arms (440) drop to release the body (300) as shown in FIG. 17B. Next, the spring (460) acts to bias the body (300) downwardly so that the microneedles are embedded in the skin located therebelow.

[0206] Next, refer to FIG. 18, which includes a thin metal annular skirt (465) fixed to the body (300) and also fixed to the housing (25). The skirt (465) is designed to intentionally buckle under an axial force so as to rapidly transition from a first state (FIG. 18A) to a second state (FIG. 18B). In the pre-activated state (FIG. 18A), the central region of the skirt (465) is disposed upwardly, thereby holding the body (300) and the microneedles above the skin (50). The user depresses the button (215) to initiate a downward movement of the body (300), which in turn snaps the skirt (465) downwardly (FIG. 18B). The body (300) is rapidly moved downwardly to embed the microneedles into the skin. The snapping action of the skirt (465) does not permit any reverse movement of the body (300) and does not permit the body (300) to stop at any intermediate vertical level between that shown in FIG. 18A and that shown in FIG. 18B. The buckling of the skirt may provide tactile feedback to the user's finger by the rapid transition between states. Audible feedback in the form of a "click" may also result from the buckling action.

[0207] Some embodiments of the device may require that the region above the microneedles be electrically insulated to avoid the wet surface of the skin (which is different from the biological fluid thereunder) from forming a conduction path between the microneedles.

[0208] As another means of controlling moisture, the absorbent material may be positioned at the micro-needle attachment portion, proximate to the micro-needle tip. In embodiments of the device for sensing applications, the material improves the subject's experience and ameliorates any problems that may be caused by fluid contact with other parts of the device, such as electronic circuitry or electrical contacts. It is configured to absorb any excess fluid that may be generated by the insertion of the micro-needles into the skin. In embodiments of the device for fluid extraction applications, the material acts as a wicking agent to transport fluid from the micro-needle site to a desired final site on the device or outside 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 micro-needles prior to insertion, the sheet includes holes through which the micro-needles pass. The holes are sized large enough to prevent the absorbent material from contacting the micro-needles during the micro-needle insertion process, but small enough to allow excess fluid exuding from the access penetration points created by the micro-needles to contact and be absorbed by the material. In other embodiments where the device is intended to be used for fluid extraction, the sheet of absorbent material either has no holes or the holes are sized such that the absorbent material contacts the micro-needles during and after insertion to assist its wicking action. In embodiments where the sheet has no holes, the micro-needles create holes as they pass through the sheet as part of the insertion process.

[0209] The device may be configured for use in and / or used for any suitable application where the micro-needles are required to be embedded in the subject's skin for an extended period of time.

[0210] 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 bound 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.

[0211] 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, and the electrical signal is generated at an electrode coated on the surface of the micro-needle or integrated into the micro-needle and transmitted along the shaft of the micro-needle to the base of the micro-needle, and an electrical connection is 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 the tip of the micro-needle, on at least a portion of the shaft of the micro-needle remote from the micro-needle, and on at least a portion of the shaft of the micro-needle proximate the tip of the micro-needle.

[0212] Micro needles may be connected to the electronic circuit configuration by various methods known in the art, such as soldering, wire wrapping, or spring-loaded pins. In one embodiment, the micro needle is attached to pass through a plate or a block of dielectric material, and the connection portion of the micro needle is positioned on or above the surface of the block or plate distal to the micro needle tip. A zebra strip connection may be used to connect the micro needle to the electronic circuit configuration to facilitate a robust connection that does not require exact alignment of the zebra connector with the micro needle end in at least one dimension.

[0213] Another potentially useful application is the delivery of active substances to the skin. The substances may mainly remain on the skin or may enter the systemic circulation. In such applications, the micro needles may be hollow and the substances are delivered through the needle lumen. Alternatively, the micro needles may be coated with the 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 micro needles themselves may be soluble in the biological fluid and may contain the active substance within their bulk such that the active substance is released as the micro needles dissolve. The active substance may be a pharmaceutical composition (e.g., small molecule, protein, peptide, or nucleic acid) for use as a vaccine, or an immunologically active composition (e.g., a collection of proteins).

[0214] A further possible application is the delivery of an electric current to the skin for the purpose of muscle stimulation or for the stimulation or inhibition of the biological processes 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.

[0215] In any of the above applications, the micro needles may be solid or hollow, as required or desired.

[0216] The length of the microneedle may be selected according to a specific application. Typically, the microneedle is required to extend at least under the stratum corneum. The depth of the stratum corneum varies by location, and the layer is, for example, 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.

[0217] In some cases, the microneedle may need to extend well below the stratum corneum and into the dermis, including the lower layers of the epidermis, the dermis, and even the subcutaneous tissue within the dermis. Again, the length of the microneedle extending beyond the device may be correspondingly set.

[0218] One of ordinary skill in the art will understand the need to be able to set the microneedle length according to the intended subject. For example, relatively short microneedles are generally required to provide access to the subcutaneous tissue of neonatal subjects, while for the same site, adult subjects require longer microneedles.

[0219] In some applications, it may be desirable 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 move one microneedle relative to the other. For example, the attachment portion may be multi-levelled with a first electrode extending from a first level and a second electrode extending from a second level.

[0220] For typical applications, the microneedle may extend outwardly from the device at 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.

[0221] Those skilled in the art will understand that the present invention described herein is susceptible to further variations and modifications other than those specifically described.

[0222] For example, the movable arm may be moved by the user squeezing or clamping the flexible portion of the device housing, by actuating a rotary lever, or by sliding an element along an incline to bias the arm downward.

[0223] The skin contact portion of the device is depicted as being strictly planar on its underside (skin contact surface), but in some embodiments, the skin contact portion of the device 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.

[0224] The space in which the microneedles extend is generally shown as a hole, but other types of spaces are envisioned. In some embodiments, the space is not a hole, and one such embodiment has microneedles that extend through a peripheral space relative to the skin contact portion.

[0225] It is understood that the present invention includes all of the foregoing variations and modifications within the spirit and scope of the present invention, and in fact includes further variations and modifications.

[0226] 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 bringing one or more protrusions into contact with the skin of a subject, comprising: one or more protrusions, each protrusion penetrating the skin; a skin contact portion defining a skin contact surface and one or more spaces allowing 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 raised from the skin contact surface; the apparatus is configured to maintain the one or more protrusions in a first state in which the apparatus cannot contact the skin of the subject until the apparatus is actuated by a user, the actuation causing the one or more protrusions to transition to a second state in which the one or more protrusions are fully embedded in the skin or enabling the one or more protrusions to transition to a second state in which the one or more protrusions are fully embedded in the skin, and the apparatus is further configured to (i) inhibit or prevent the transition of the one or more protrusions towards the first state after the actuation or (ii) require an intentional act by the user or another user to move the one or more protrusions towards the first state after the actuation; Apparatus.

2. The apparatus according to claim 1, further comprising a holding portion configured to hold the skin contact surface in contact with the skin during use.

3. The apparatus according to claim 1 or 2, wherein the movable portion is configured to move from the first position to the second position along a non-linear path.

4. The apparatus according to claim 3, wherein the non-linear path is generally arcuate.

5. The apparatus according to any one of claims 1 to 4, wherein the movable portion has a connection end and a free end.

6. The apparatus according to claim 5, wherein the free end moves a longer distance than the connection end.

7. The apparatus according to any one of claims 3 to 6, wherein the non-linear path is described with reference to the free end.

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

9. The degree of the arc is less than about 45°, 40°, 35°, 30°, 25°, 20°, 15°, 14°, 13°, 12°, 11°, 10°, 9°, 8°, 7°, 6°, or 5°, and the device according to any one of claims 4 to 8.

10. The movable part has a pivoting part, a hinge part, a bending part, or a mounting part, and the device according to any one of claims 1 to 9.

11. The movable part is associated with a mounting part, and the device according to any one of claims 1 to 10.

12. During use, the mounting part is stationary, and the movable part is movable relative to the mounting part, and the device according to claim 11.

13. The mounting part enables the movable part to pivot, hinge, bend, or adhere, and the device according to claim 11 or 12.

14. The mounting part is in a fixed spaced relationship with respect to the skin contact surface, and the device according to any one of claims 11 to 13.

15. The mounting part is spaced from the skin contact surface by about 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, or less than 2 mm, and the device according to any one of claims 11 to 14.

16. The mounting part is generally transverse to the movable part, and the device according to any one of claims 11 to 15.

17. The device further includes a user-activatable release part, and the user-activatable release part is configured to hold the movable part in the first position until user activation of the release part, and when the user activates, the movable part is released and is enabled to move to the second position, and the device according to any one of claims 1 to 16.

18. The device further includes a locking part configured to lock the movable part when in the second position, and the device according to any one of claims 1 to 17.

19. The device is configured such that the movement of the movable part from the first position to the second position requires a motive force derived internally and / or externally with respect to the device, and the device according to any one of claims 1 to 18.

20. The internal motive power for the device is derived from a spring, an elastically deformable member, a shape memory member, or other biasing means, and the external motive power for the device is derived from a user, the device according to claim 19.

21. The device according to any one of claims 1 to 20, wherein the device does not have an internal motive power generator configured to move the movable part from the first position to the second position.

22. The device according to any one of claims 1 to 21, wherein the holding part 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.

23. The device according to claim 22, wherein the dermatologically acceptable composition is an adhesive or a functional equivalent thereof.

24. The device according to any one of claims 1 to 23, wherein the holding part is configured to mechanically hold the skin contact surface in contact with the skin.

25. The device according to claim 24, wherein the holding part is selected from any one or more of a strap, a band, a belt, a clamp, a grip, a necktie, a fastener, a sleeve, a stocking, a sock, a glove, a brimless hat, a hat with a brim, an undershirt, a singlet, a shirt, a bra, a top, pants, a scarf, a ring, glasses, and a choker.

26. The device according to any one of claims 1 to 25, wherein the one or more protruding parts are mechanically directly or indirectly connected to the movable part.

27. The device according to any one of claims 1 to 26, wherein the one or more protruding parts are wires, needles, and / or microneedles.

28. The device according to claim 27, wherein the one or more protruding parts form an array.

29. The device according to any one of claims 1 to 28, wherein the one or more protruding parts are of a sufficient length to be able to contact the epidermis, dermis, or hypodermis of the subject.

30. The one or more protruding portions are configured to, during use, transmit current to the skin, transmit current from the skin, transmit current through the skin, transmit sound waves to the skin, transmit sound waves from the skin, transmit sound waves 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 fluid or tissue from the skin, deliver a biologically active substance to the skin, or introduce a sensing substance into the skin, the apparatus according to any one of claims 1 to 29.

31. The one or more protruding portions are each conductive, and the apparatus further includes a circuit having an audible, visual, or tactile indicator, the circuit being configured to activate the indicator when the one or more protruding portions contact a conductive fluid naturally present on the skin, the apparatus according to any one of claims 1 to 30.

32. The circuit includes at least two protruding portions, the circuit being 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 indicator, the apparatus according to claim 31.

33. The circuit includes one protruding portion and at least one conductive pad disposed with respect to the skin, the circuit being configured to be completed by the pad and the protruding portion that are in electrical communication with the conductive fluid naturally present on the skin so as to activate the indicator, the apparatus according to claim 31.

34. The apparatus includes a housing, the housing having dimensions such that when the apparatus is applied to the skin, the movable portion is in the second position, and any portion of each of the one or more protruding portions that rises from the skin contact surface is embedded in the skin, most or substantially all of the housing 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 33.

35. The device according to any one of claims 1 to 34, configured to be used over 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.

36. The device according to any one of claims 1 to 35, wherein the one or more protruding portions are configured to be inseparable from the device or not separable from the device without the assistance of a tool.

37. The device according to any one of claims 1 to 36, wherein the movable portion and the mounting portion are integral.

38. The device according to claim 37, wherein the integral movable portion and mounting portion are manufactured from an elastically deformable material.

39. The device according to claim 37 or 38, wherein the integral movable portion and mounting portion are part of a circuit board of the device.

40. The movable portion is biased towards the second position and is maintained in the first position against the bias by the user-operable release portion until actuation of the release portion. When the release portion is actuated, the movable portion is released and is enabled to move to the second position. The device according to any one of claims 17 to 39.

41. The user-operable 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 17 to 39.

42. The device according to any one of claims 1 to 41, wherein the movable portion is in a hinge-connected relationship with the skin contact portion.

43. The device according to claim 42, wherein the hinge is disposed in or towards a peripheral region of the movable portion and the skin contact portion.

44. The release portion includes a member configured to maintain the movable portion in the first position, but is removable or deformable by the user so as to allow the movable portion to move to the second position, the apparatus according to any one of claims 17 to 43.

45. The apparatus according to claim 44, wherein the member is removable by sliding it generally across the skin contact portion.

46. The member is generally wedge-shaped, and the apparatus includes a hinge that associates the movable portion with the skin contact portion, 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, the apparatus according to claim 45 or 45.

47. The apparatus according to any one of claims 44 to 46, wherein the release portion is removable from the apparatus and includes a gripping portion that facilitates removal by hand.

48. The apparatus according to any one of claims 1 to 47, wherein the transition of the one or more protrusions from the first state to the second state is achievable by a single actuation performed by the user on a device component or by movement of a device component by the user in a single direction.

49. The single actuation or the movement in a single direction is selected from pushing, pulling, depressing, compressing, rotating, twisting, bending, squeezing, stretching, separating, breaking, joining, rotating, redirecting, hitting, tapping, and vibrating, the apparatus according to claim 48.

50. The apparatus according to any one of claims 1 to 49, wherein the transition, once initiated, is configured to be (i) non-reversible by the user or (ii) require an intentional act by the user or another user.

51. The apparatus according to any one of claims 1 to 50, wherein the transition is configured to be completed in about 1 second, 900 milliseconds, 800 milliseconds, 700 milliseconds, 600 milliseconds, 500 milliseconds, 400 milliseconds, 300 milliseconds, 200 milliseconds, 100 milliseconds, 90 milliseconds, 80 milliseconds, 70 milliseconds, 60 milliseconds, 50 milliseconds, 40 milliseconds, 30 milliseconds, 20 milliseconds, 10 milliseconds, 9 milliseconds, 8 milliseconds, 7 milliseconds, 6 milliseconds, 5 milliseconds, 4 milliseconds, 3 milliseconds, 2 milliseconds, or less than 1 millisecond.

52. The apparatus according to any one of claims 1 to 51, wherein the transition is configured to be substantially instantaneous.

53. The apparatus according to any one of claims 1 to 52, wherein the start or completion of the transition is configured to be associated with a tactile, auditory, or visual feedback signal to the user.

54. The apparatus according to any one of claims 1 to 53, wherein the one or more protruding portions extend from the body, and the body is subjected to an action during the transition.

55. The apparatus according to any one of claims 1 to 54, wherein the transition includes movement of the one or more protruding portions from a first position to a second position.

56. Including a snap mechanism, the snap mechanism is configured to prevent movement of the one or more protruding portions from the first position until a user applies at least a threshold level of force to a component of the apparatus by an actuation, and once the at least threshold level of force is applied, the one or more protruding portions are caused to transition to or be capable of transitioning to the second position in about 100 milliseconds, 90 milliseconds, 80 milliseconds, 70 milliseconds, 60 milliseconds, 50 milliseconds, 40 milliseconds, 30 milliseconds, 20 milliseconds, 10 milliseconds, 9 milliseconds, 8 milliseconds, 7 milliseconds, 6 milliseconds, 5 milliseconds, 4 milliseconds, 3 milliseconds, 2 milliseconds, or less than 1 millisecond, or substantially instantaneously. The apparatus according to claim 55.

57. The apparatus according to claim 56, wherein the snap mechanism includes an elastically deformable formation that must be deformed to allow the one or more protruding portions to move from the first position to the second position.

58. The apparatus according to claim 57, wherein the elastically deformable forming part is associated with the one or more protruding parts or another component of the apparatus.

59. The apparatus according to claim 58, wherein the another component is a component that remains stationary during operation.

60. The apparatus according to claim 58 or 59, wherein the another component is the housing of the apparatus, a component of the apparatus that contacts the skin of the subject to which the apparatus is applied, or a component of the apparatus through which the one or more protruding parts extend.

61. The apparatus according to any one of claims 56 to 60, wherein the snap mechanism locks the one or more protruding parts in the second position after operation of the apparatus.

62. The apparatus according to any one of claims 56 to 61, comprising a main body, wherein the one or more protruding parts extend from the main body, and the snap mechanism includes a part extending from the main body.

63. Biasing means is included, which is configured to maintain the one or more protruding parts in the first position until actuation occurs, or to rapidly move the one or more protruding parts from the first position to the second position, or to maintain the one or more protruding parts in the second position after actuation occurs, in the apparatus according to any one of claims 55 to 62.

64. The apparatus according to any one of claims 55 to 63, comprising one or more catches, wherein the one or more catches are configured to allow movement of the one or more protruding parts toward the second position in the movement of the one or more protruding parts from the first position to the second position, but to prevent movement of the one or more protruding parts back toward the first position.

65. A method of contacting a protrusion with the skin of a subject, comprising: providing an apparatus according to any one of claims 1 to 64; contacting the skin contact surface of the apparatus with the skin; moving the movable part from the first position to the second position in a non-linear path or enabling the movable part to move from the first position to the second position in a non-linear path. Method.

66. The method according to claim 65, 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.

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