Needle-based device with power management function

Abstract

An electrochemical sensor device for introducing a needle electrode into the skin of a subject to contact a target body fluid or tissue and detect a target analyte. The device has a movable part for biasing the needle electrode against the skin of the subject and a power management function for supplying operating power to the sensor electronics before and after the device is disposed.

Description

Technical Field

[0001] The present invention generally relates to an apparatus useful for introducing and holding a needle into the skin of a subject. The apparatus is configured to be simple, lightweight, and low profile so as not to be relatively obstructive to the subject. Further, the apparatus has a power management function such that it is automatically powered on when applied to the subject.

Background Art

[0002] Advances in microfabrication technology in the 1990s made it possible to mass-produce microneedle devices for medical use.

[0003] A single microneedle typically has a length of 150 to 1500 μm, a width of 50 to 250 μm, and a tapered tip with a thickness of 1 to 25 μm. In the context of biosensor devices, microneedles can be conductive and function as working electrodes, counter electrodes, or reference electrodes. Microneedles can be manufactured from metals, silicon, polymers, glass, or ceramics, 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] As a working electrode in an electrochemical biosensor, a microneedle can be conductive and may be coated with a redox-modified aptamer or enzyme configured to interact with specific analytes in biological fluids such as interstitial fluid or blood. Typically, the biosensor is interrogated (e.g., square wave voltammetry) by the application of a potential. The peak current passing through the working electrode is measured, and the value is used to determine the amount of analyte present around the working electrode.

[0005] The prior art discloses numerous devices for inserting microneedles into the skin of a subject. Such devices are typically configured to facilitate the application of microneedles by the subject in a non-clinical environment such as at home. Ease of use and reproducibility are the primary objectives of these devices.

[0006] Some devices are specialized only for the application of microneedles, and once that task is completed, the device is removed along with the microneedle. Other prior art devices are configured to be separated from the microneedle, thereby allowing the microneedle to remain in place within the skin for a period after introduction. Within the skin, the microneedle can sense increases and decreases in the concentration of analytes in the interstitial fluid.

[0007] Yet another type of prior art device is configured to introduce a microneedle, and the device (including the microneedle) remains in place on the subject for a period of time. These devices provide simplicity to the subject, but nevertheless present numerous problems.

[0008] One problem is that such devices are generally obtrusive and are easily recognized by the subject. The device can catch on clothing or other nearby objects, causing complete or partial dislodgment. These devices need to be worn overnight, and significant discomfort occurs when the subject rolls over on the device.

[0009] A further problem is that prior art devices are complex, having a large number of individual components. This increases the cost of the device and also increases the tendency for failure. The large number of components also increases the weight of the device, thereby increasing the obtrusiveness to the subject. It has been found that the discomfort associated with the weight increases proportionally to the period during which 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 replaced several times during that period, but the problem remains of the subject wearing a heavy device over a long period.

[0010] A further problem arises in that the subject may not be certain whether the microneedles have properly penetrated the skin in the first instance and, further, whether they have remained properly embedded in the skin over time. Prior art devices typically have a housing, the lower surface of which is at the same height as the surface of the skin. Due to the presence of the housing, it is difficult, if not impossible, for the subject to view the surface of the skin and confirm proper microneedle embedding. In case of doubt, the device can be removed and a new device applied to the skin. If the microneedles have in fact been properly inserted, replacing the device is wasteful.

[0011] As described above, the biosensor device can obtain information by applying a potential to the needle electrode. This requires a power source, which is often supplied by a battery incorporated in the device. To conserve battery power, the device is typically supplied in a powered-off state or a "sleep" state using minimal power. Prior to use, the device must typically be actively powered-up by the user, usually by consciously activating a dedicated "on" switch.

[0012] Prior art methods for powering an electronic device include a switch that requires some dedicated physical action by the user. The device can be powered on, for example, by pressing or sliding a switch. The switch often exists through an opening in the device housing, presenting the possibility of ingress of water, atmospheric water vapor, body fluids, or some other source of moisture.

[0013] It is highly desirable for a needle-based biosensor device to be powered on before the electrodes are inserted into the skin and subcutaneous layer. If the electrodes are inserted before the device is powered on, the user is forced to activate the power switch when the electrodes are already inserted into the dermal tissue. Activating the switch can cause movement of the inserted electrodes, which may lead to tissue damage and even complete or partial detachment of the electrodes.

[0014] In any case, the need for the user to power on the needle-based biosensor device introduces complexity to the operation. Such complexity can be difficult, especially when the device is designed to be used by the subject itself. The subject may be a child, very elderly, or in some incapacitated state, resulting in difficulty in arranging a somewhat complex device. Any error in the operation of the device can have negative consequences for the subject, for example, when the device is not powered on during application and thus cannot provide important outputs such as blood glucose levels.

[0015] One aspect of the present invention is to provide an improvement over prior art needle-based devices. The improvement can be made in any one or more of protrusion, size, weight, complexity, cost, and the ability to monitor unauthorized implantation. Further improvements can be made in the means by which the device is powered on. The improvement can be provided only by one embodiment of the present invention. Depending on the situation, the present invention may not provide any improvement and instead may only provide a useful alternative to prior art devices.

[0016] The descriptions of documents, acts, materials, devices, articles, etc. are included in this specification only for the purpose of providing context for the present invention. None of these items, or all of them, are intended to imply or indicate that they formed part of the prior art base or were common general knowledge in the field related to the present invention prior to the priority date of each claim of this application.

Summary of the Invention

[0017] In a first aspect, which is not necessarily the broadest aspect, the present invention provides an apparatus for bringing one or more protrusions into long-term contact with a target skin, the apparatus comprising: one or more protruding portions each configured to penetrate the skin; a skin contact portion defining a skin contact surface and one or more spaces through which the one or more protruding portions extend therethrough; a movable portion configured to move the one or more protruding portions from a first position behind the skin contact surface to a second position protruding from the skin contact surface; an electronic device configured to perform the functions of the apparatus having a power source; an enclosure around the electronic device and the power source; and a power regulator; and having the power regulator is first operable such that the electronic device is in a first state in which it consumes no power or consumes a non-operating amount of power, and the electronic device takes a second state in which it consumes an operating amount of power, and the apparatus is configured such that the power regulator is transitioned from the first state to the second state without a dedicated power-on operation performed by the user during the normal placement process of the apparatus.

[0018] In one embodiment of the first aspect, the apparatus has a holding portion configured to hold the skin contact surface in contact with the skin during use.

[0019] In one embodiment of the first aspect, the movable portion is configured to move from the first position to the second position along a non-linear path.

[0020] In one embodiment of the first aspect, the non-linear path is a substantially arcuate path.

[0021] In one embodiment of the first aspect, the movable portion has a connection end and a free end.

[0022] In one embodiment of the first aspect, the free end moves a longer distance than the connection end.

[0023] In one embodiment of the first aspect, the non-linear path is described by referring to the free end.

[0024] 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.

[0025] 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°.

[0026] In one embodiment of the first aspect, the movable part has a swiveling part, a hinge part, a bending part, or an attachment part.

[0027] In one embodiment of the first aspect, the movable part is associated with a mounting part.

[0028] In one embodiment of the first aspect, during use, the mounting part is stationary and the movable part is movable relative to the mounting part.

[0029] In one embodiment of the first aspect, the mounting part includes a part that enables the movable part to swivel, hinge, bend, or attach.

[0030] In one embodiment of the first aspect, the mounting part can be spaced apart from the skin contact surface.

[0031] In one embodiment of the first aspect, the mounting part can be spaced apart from the skin contact surface by a distance of less than about 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, or 2 mm.

[0032] In one embodiment of the first aspect, the mounting part is generally transverse to the movable part.

[0033] In one embodiment of the first aspect, the device further has 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 of the release portion, the movable portion is released and enabled to move to a second position.

[0034] In one embodiment of the first aspect, the device further has a locking portion configured to lock the movable portion when in the second position.

[0035] In one embodiment of the first aspect, the device is configured such that movement of the movable portion from the first position to the second position requires a motive force generated from within and / or outside the device.

[0036] In one embodiment of the first aspect, the motive force within the device is due to a spring, an elastically deformable member, a shape memory member, or other biasing means; and the motive force outside the device is due to the user.

[0037] In one embodiment of the first aspect, the device lacks an internal motive force generator configured to move the movable portion from the first position to the second position.

[0038] In one embodiment of the first aspect, the holding portion is or includes a dermatologically acceptable composition disposed on or around the skin contact surface.

[0039] In one embodiment of the first aspect, the dermatologically acceptable composition is an adhesive or a functional equivalent thereof.

[0040] In one embodiment of the first aspect, the holding portion is configured to mechanically hold the skin contact surface in contact with the skin.

[0041] In one embodiment of the first aspect, the holding portion 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 cap, a hat, pants, a tank top, a shirt, a bra, a top, trousers, a scarf, a ring, glasses, and a choker.

[0042] In one embodiment of the first aspect, one or more protruding portions are mechanically connected directly or indirectly to the movable portion.

[0043] In one embodiment of the first aspect, one or more protruding portions are a wire(s), a needle(s), and / or a microneedle(s).

[0044] In one embodiment of the first aspect, one or more protruding portions form an array.

[0045] In one embodiment of the first aspect, one or more protruding portions are of a sufficient length to be able to contact the epidermis, dermis, or subcutaneous tissue of the subject.

[0046] In one embodiment of the first aspect, one or more protruding portions are configured to function to pass an electric current to, from, or through the skin, transmit a sound wave to, from, or through the skin, conduct light to, from, or through the skin, transfer heat to, from, or through the skin, sample a fluid or tissue from the skin, deliver a biologically active substance to the skin, or introduce an analyte sensing substance to the skin during use.

[0047] In one embodiment of the first aspect, one or more protruding portions are each conductive, and the device further has a circuit with an audio, visual, or tactile indicator, and the circuit is configured to activate the indicator when one or more of the protruding portion(s) come into contact with a conductive fluid naturally present on the skin.

[0048] In one embodiment of the first aspect, the circuit includes at least two protruding portions, and the circuit is configured to be completed by the at least two protruding portions contacting a conductive fluid that naturally exists on the skin so as to activate the indicator.

[0049] In one embodiment of the first aspect, the circuit has one protruding portion and at least one conductive pad disposed on the skin, and the circuit is configured to be completed by the protruding portion and the pad being in electrical communication with a conductive fluid that naturally exists on the skin so as to activate the indicator.

[0050] In one embodiment of the first aspect, when the device is applied to the skin, the movable part is in the second position, and when any part of each of the one or more protruding portions protruding from the skin contact surface is embedded in the skin, the housing includes a housing dimensioned to extend over the skin at about 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm or 20 mm or less for most or substantially all parts.

[0051] In one embodiment of the first aspect, a long period is greater 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.

[0052] In one embodiment of the first aspect, the device is configured such that one or more protruding portions are non-detachable from the device or cannot be separated without the assistance of tools.

[0053] In one embodiment of the first aspect, the movable part and the attachment part are integral.

[0054] In one embodiment of the first aspect, the integral movable part and attachment part are manufactured from an elastically deformable material.

[0055] In one embodiment of the first aspect, the integral movable part and the attachment part are part of the circuit board of the device.

[0056] In one embodiment of the first aspect, the movable part is biased towards a second position and is held in the first position by a user-operable release part against the bias 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.

[0057] In one embodiment of the first aspect, the user-operable release part is a ledge configured to hold the movable part in the first position, and the motive force provided by the user deforms the ledge and / or the movable part such that the movable part is released from the ledge and enabled to move to the second position.

[0058] In one embodiment of the first aspect, the movable part is hingedly coupled to the skin contact part.

[0059] In one embodiment of the first aspect, the hinge is disposed at or towards the peripheral region of the movable part and the skin contact part.

[0060] In one embodiment of the first aspect, the release part has a member configured to maintain the movable part in the first position, but is removable or deformable by the user such that the movable part is enabled to move to the second position.

[0061] In one embodiment of the first aspect, the member is removable by sliding substantially across the skin contact part.

[0062] In one embodiment of the first aspect, the member is substantially wedge-shaped, the device has a hinge associating the movable part with the skin contact part, the thin part of the wedge is disposed proximal to the hinge, and the thick part of the wedge is disposed distal to the hinge.

[0063] In one embodiment of the first aspect, the release portion is removable from the device and has a grip portion that facilitates manual removal.

[0064] In the second aspect, the present invention provides a method for 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 subject, and moving or enabling the movable portion to move from a first position to a second position along a non-linear path.

[0065] In one embodiment of the second aspect, the device remains in contact with the skin for a period exceeding 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.

[0066] In the third aspect, the present invention provides a device for contacting one or more protrusions with the skin of a subject, the device comprising: one or more protruding portions each configured to penetrate the skin; a skin contact portion defining one or more spaces through which the skin contact surface and the one or more protruding portions extend; a movable portion configured to move the one or more protruding portions from a first position behind the skin contact surface to a second position protruding from the skin contact surface; a holding portion configured to hold the skin contact surface in contact with the skin during use; and a user-actuable release portion configured to hold the movable portion in the first position until user actuation of the release portion, and upon user actuation of the release portion, enabling the movable portion to be released and move to the second position.

[0067] In one embodiment of the third aspect, the release portion has a member configured to maintain the movable portion in the first position, but is removable or deformable by the user to enable the movable portion to move to the second position.

[0068] In one embodiment of the third aspect, the member is removable by sliding generally across the skin contact portion.

[0069] In one embodiment of the third aspect, the member is generally wedge-shaped, the device has a hinge that associates 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.

[0070] In one embodiment of the third aspect, the release portion is removable from the device and has a grip portion to facilitate manual removal.

[0071] In the fourth aspect, the present invention provides a method for contacting a protrusion with the skin, the method comprising providing a device of any embodiment of the third aspect, contacting the skin contact surface of the device with a target, and moving or enabling movement of the movable portion from a first position to a second position by actuating a user-actuable release portion.

[0072] In one embodiment of the fourth aspect, the power regulator is transitioned from a first state to a second state by an action performed by the user during the normal placement of the device, and the action is not a dedicated power supply action.

[0073] In one embodiment of the fourth aspect, the actions are selected from the group consisting of opening the package in which the device is contained, separating the device from a packaging item, separating the device from a protective item, separating the guard portion of the device from the device, separating the spacer portion from the device, separating the blocking portion from the device, exposing a portion of the device, moving a first portion of the device relative to a second portion of the device, opening the device, closing the device, sliding a first portion of the device relative to a second portion of the device, moving the hinge portion of the device, contacting a portion of the device with a fluid, and contacting a portion of the device with a target.

[0074] In one embodiment of the fourth aspect, the power regulator is configured to sense operation.

[0075] In one embodiment of the fourth aspect, the power regulator is in electrical communication with the processor of the device, and when the power regulator transitions to the second state, an electrical signal is sent to the processor so that the electronic device consumes or is allowed to consume power at the amount of operation.

[0076] In one embodiment of the fourth aspect, the power regulator has or is in electrical communication with a sensor configured to sense operation.

[0077] In one embodiment of the fourth aspect, the sensor or the power regulator detects an electric field, an electromagnetic field, a magnetic field, light, strain, orientation, acceleration, movement, thermal energy, conductivity, electrical resistance, capacitance, contact with human skin, pressure, strain, tension, torsion, compression, or movement.

[0078] In one embodiment of the fourth aspect, the sensor or the power regulator has a Hall effect sensor or another type of magnetic field sensor.

[0079] In one embodiment of the fourth aspect, the sensor or the power regulator has an electrical switch.

[0080] In one embodiment of the fourth aspect, the electrical switch has two electrically separated electrical contacts present with respect to the environment around the device enclosure; and a movable conductive portion that can contact both of the two separate electrical contacts so as to close the switch, and the movement of the movable conductive portion opens and closes the switch.

[0081] In one embodiment of the fourth aspect, the switch is disposed within the device enclosure.

[0082] In one embodiment of the fourth aspect, the power regulator and / or the sensor is substantially impermeable to fluids or vapors.

[0083] In one embodiment of the fourth aspect, the device enclosure comprises a flexible portion through which a power regulator is operable.

[0084] In one embodiment of the fourth aspect, the flexible portion is substantially impermeable to fluids or vapors.

[0085] In one embodiment of the fourth aspect, the flexible portion forms an interface with the main portion of the device enclosure that is substantially impermeable to fluids or vapors.

[0086] In one embodiment of the fourth aspect, the device lacks an actuator that requires a dedicated human action to transition the power regulator from a first state to a second state.

[0087] In one embodiment of the fourth aspect, the device has a working electrode configured to contact a biological fluid, either in vivo or in vitro, and detect an analyte therein.

[0088] In one embodiment of the fourth aspect, the working electrode is at least one wire, needle, or microneedle.

[0089] In the fifth aspect, the present invention provides: providing a device of any embodiment of the first aspect, and enabling the power regulator to transition from a first state to a second state in response to an action performed by a user during the normal placement process of the device, and provides a method of placing a device.

[0090] In one embodiment of the fifth aspect, the operations are selected from the group consisting of: opening the package containing the device, separating the device from the packaging item, separating the device from the protective item, separating the guard portion of the device from the device, separating the spacer portion from the device, separating the blocking portion from the device, exposing a part of the device, moving a first part of the device relative to a second part of the device, opening the device, closing the device, sliding a first part of the device relative to a second part of the device, moving the hinge portion of the device, contacting a part of the device with a fluid, and contacting a part of the device with a target.

Brief Description of the Drawings

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[0112] Unless otherwise indicated herein, features of the drawings labeled with the same number are considered to be the same feature, or at least functionally similar features, when used across different drawings.

[0113] The drawings are not drawn to scale and are not presented as a complete and exact representation of various embodiments.

Best Mode for Carrying Out the Invention

[0114] After considering this description, those skilled in the art will understand 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, it is understood that these embodiments are presented by way of example only and are not limiting. Therefore, 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 or any embodiments covered by the actual claims.

[0115] Throughout the description and claims of this specification, the words "comprise", "comprises" and variations such as "comprising" are not intended to exclude other additional elements, components, integers or steps.

[0116] References throughout this specification to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Thus, the appearances of the phrases "one embodiment" or "an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, although they may.

[0117] As used herein, positional terms such as "lateral", "across", "on", "above", "below", "high", "low", "upward", "down", "plan view", etc. should be considered with reference to the device of the invention when applied to an upward-facing region of the skin of an object, such as the upper surface of a human thigh when the human is sitting on a chair. The device can be applied to regions of the skin having an orientation different from the upright orientation described above, in which case those skilled in the art can adequately reformulate the above positional terms.

[0118] As used herein, terms such as "power on" and "power on" are intended to include the transition of the device electronics from a state where power is not fully supplied to an operating state where power is fully supplied, and the transition of the device from a low power state (such as a "sleep" state) to an operating state where power is fully supplied.

[0119] The term "power regulator" is intended to include single or multiple component means that control, for example, the amount of power supplied to or available for the electronics of a device, or that function to control the amount of power consumed by the electronics. A power regulator can directly control the current, for example, by modulating the current available for consumption by the device electronics, or can function as a simple switch that supplies all or zero power to the electronics. The scope of the term "power regulator" also includes any means that can transition the device from a sleep mode to an operating mode.

[0120] "Biological fluid" can be any biological fluid of a subject, including but not limited to interstitial fluid (ISF), blood, saliva, lacrimal gland secretions, milk secretions, nasal mucus, tracheal secretions, bronchial secretions, alveolar secretions, gastric secretions, gastric contents, glandular secretions, vaginal secretions, uterine secretions, prostatic secretions, semen, urine, sweat, cerebrospinal fluid, glomerular filtrate, liver secretions, bile, or exudate, any of which can come into contact with the needle electrode of an electrochemical sensor in vivo. "Tissue" includes a volume containing one or more cells.

[0121] The term "subject" is used to refer to an animal (including humans and non-human animals) to which the device can 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 not necessarily.

[0122] Unless the context of use clearly indicates a contrary intention, the terms "needle", "microneedle" and "wire" are used interchangeably. Each is functionally identical or similar and can be inserted into the skin of a subject to contact biological fluid.

[0123] Various different embodiments of the present invention are disclosed herein (by the drawings or the written description), and the embodiments have one or more features disclosed in that context. It will be understood that there is no intention to limit the application of a particular feature or combination of features to the embodiments in which it is disclosed. For example, a first embodiment may be disclosed as including features A and B, and a second embodiment may be disclosed as including features C and D. Embodiments having any one, two, three, or four of features A, B, C, and D in any combination within the scope of the present invention are intended to be included.

[0124] However, it will be apparent to those skilled in the art that certain combinations are less preferred or are actually contraindicated. For example, if feature B requires feature A to operate, an embodiment including the combination of features B, C, and D may be infeasible.

[0125] The present invention is based at least in part on the discovery that an improved or alternative extended wear microneedle device is provided, the device having a movable portion that biases microneedles against the skin of a subject, an optional release portion that enables movement, and a power regulator that powers the device during a normal placement process. Associated operations that occur during the normal placement process may include operations related to the movable portion or the release portion, or some other operation. The power regulator may transition from a power-off or low-power (sleep) mode to an operating mode during the normal placement process of the device. Such a device liberates the user (who may be the subject to which the device is applied or some other individual such as a caregiver) from having to remember to power on the device before use. Separate from having to remember to power on the device, the user is also liberated from having to perform a dedicated power-on operation such as actuating a switch.

[0126] The movable part can move along a non-linear path. Further, the non-linear path can be of limited length, and the path can be of a limited number of arcs. With this configuration, the main movable part of the device only requires movement within a limited vertical range to attach and insert the microneedles into the skin of the subject. The limited range of movement allows the housing of the device to have a relatively low profile when viewed laterally. In this way, the device rises to a relatively low height above the skin and is thus less conspicuous to the subject. Nevertheless, the limited range of movement can be related to the power regulator and thus can be involved in powering on the device in some way.

[0127] Furthermore, the non-linear path of the movable part allows for the use of a simplified mechanism. For example, the movable part can be moved by a simple bending or hinge mechanism. These mechanisms require a relatively small number of components and, overall, enable the development of a smaller, lighter, simpler, more reliable, and less expensive device.

[0128] Certain embodiments of the present invention have additional features that provide further advantages over the prior art or more useful alternatives when used alone or in combination with other features. Such embodiments are more fully described by reference to the non-limiting preferred embodiments described below.

[0129] Refer to FIG. 1, which shows a basic form of the present device (10) having a microneedle array (one microneedle is marked as 15) attached to a movable part that is an elastically deformable arm (20) in this embodiment. The arm (20) is biased to take a straight shape (20b), but initially, it is presented to the user in a state where the arm is curved upward and bent, as shown by the dashed line indication (20a).

[0130] The device (10) includes a rigid housing (25) having on its underside a skin contact portion (30) that defines a downwardly facing skin contact surface (35). The surface (35) is placed on the skin of the subject and is held there by areas of dermatologically acceptable adhesives (40a, 40b). Suitable adhesives can typically withstand water so that the subject can bathe normally. The adhesives typically have sufficient adhesiveness to prevent separation that may occur during the course of daily activities such as wearing clothes, undressing, sleeping, doing housework, light to moderate intensity exercise, and brushing against objects while walking. The level of adhesion is typically not so great as to cause difficulty, discomfort, pain, irritation, or skin damage when removing the device.

[0131] Exemplary adhesives are synthetic rubber adhesives or pressure-sensitive acrylic adhesives of the type used in medical tapes. A double-sided medical tape such as 3M (trademark) 1577 tape, where one side adheres to the device and the other side adheres to the skin of the subject, can be used.

[0132] The skin contact portion (30) has a space (45) whose margins are marked (45a) and (45b). The space (45) provides respective passages through which the microneedles (15) pass and enables the distal regions of the microneedles to penetrate and embed in the underlying skin (50) when the arms (20) are in the straight position (20b).

[0133] The arm (20) is held in a bent state by a protrusion (55) that functions as a release means. When the user wants 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) bears against the protrusion (55), and since the protrusion (55) has the ability to deform (is made of a rubber-like material or is formed, for example, by flexible protrusions on the inner surface of the housing (25)), it bends downward under the force to release the edge of the arm (20a). The elastic properties of the arm (20a) cause it to quickly return to its biased straight position (20b), thereby pushing the microneedle (15) into the underlying skin (50). The protrusion (55) is configured to exhibit sufficient elasticity to resist the biasing force of the arm (20a), but its elasticity is not sufficient to resist the downward force applied by the button (55) when depressed.

[0134] In the embodiment of FIG. 1, one end of the arm (20) is fixed to the housing (25) by a fastener (65). The arm (20) is flexible, but its flexibility is not so high that it easily moves away from the position (20b) when in a predetermined position on the target skin (50). As will be appreciated, any movement of the arm (20) away from the position (20b) can cause the microneedle (15) to be withdrawn from the skin (50). Considering the biasing of the arm (20) towards the position (20b), there may be no need for a locking mechanism to maintain the arm in the position (20b). However, if desired, a suitable locking mechanism is described below for the embodiment of FIG. 2A.

[0135] Figure 2A shows an alternative basic form of the device (200) where the arm (205) is rigid and is hinge-coupled 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 protrusion (55) functions as a 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 protrusion (55), bending the protrusion (55) and thereby releasing the free end of the arm (205a). The button (215) is continuously pressed by the user until the arm assumes the position (205b) where the microneedle (215) is embedded in the skin (50). Here too, the point on the free end of the arm (205a) moves along a non-linear path, and in this embodiment, the path is an arc that is a segment of a circle, with the origin of the circle at the hinge pin (210).

[0136] It will be understood that the hinge configuration of the embodiment of Figure 2A does not provide resistance to the hinge movement of the arm (205) 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 it is in place. Accordingly, a locking mechanism is provided to maintain the arm in the position (205b). The mechanism has a deformable latch (220), which is manufactured, for example, from a material with a certain degree of flexibility or an internal protrusion formed from the housing (25) material. The latch (220) has an inclined upper surface and, when in contact with the rigid arm (205), the entire latch (220) is forced to bend to the left (as shown in the figure) under the force applied by the user via the button (215) and the inclined upper surface. When the end of the arm (205) clears the lower corner of the inclined upper surface, the latch (220) returns to its normal upright position (shown in the figure), and the free end of the arm (205b) seats firmly in the recess at the base of the latch (220).

[0137] An alternative to the embodiment of FIG. 2A is shown in FIG. 2B. In FIG. 2B, the device (200) lacks an upper housing. The arm (205a) is maintained in a predetermined position by release means (55), which in this embodiment is removable by the user when the device (200) is applied to the subject. After removal of the release means (55), the arm (205a) is pushed downward by the user so as to take a second position (205b).

[0138] Note that in the embodiments of FIGS. 1, 2A and 2B, when released from the protrusion (55), the free end of the arm (20 or 205) moves non-linearly as it returns to its biased position (20b). If a single point on the free end of the arm (20 or 205) is considered, that point moves along a non-linear path that describes an arc. In the context of the present invention, the terms "arc", "bow" and similar terms refer to a curve joining any two points. The term "arc" is in some embodiments a segment of a circle (see for example the embodiment of FIG. 2A), but should not be construed restrictively as meaning only a segment of a circle.

[0139] 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 short distance when transitioning from the first position to the second position. Indeed, in these embodiments (and certain other embodiments), the device is intentionally configured such that the arm cannot move along a path that is outside the outer path between the first and second positions. In other words, the device can be configured such that the arm cannot move along any path that is outside the shortest distance between the first and second positions.

[0140] By providing a limitation on the path along which the arm can move, advantages are provided insofar as the height of the device is also limited (in the vertical direction as depicted). Thus, the device can take a low-profile that extends only a relatively short distance over the skin of the subject (in a dimensional sense).

[0141] Next, referring to FIGS. 3A and 3B, a preferred apparatus is shown that is generally configured in accordance with the embodiment of FIG. 1 and is operable to generally conform to the embodiment of FIG. 1. The arm (20) is integrally formed with a PCB (65) that carries various electronic components necessary for the operation of the apparatus. The PCB material is elastically deformable such that the arm (having a microneedle attached to its end) bends upward when pulled to position the arm in a first position, but when released, assumes a second position due to the natural biasing of the arm towards the second position.

[0142] The arm (20) is maintained in the first position by the end of the arm (20) that rests on the protrusion (55), as most clearly shown in FIG. 1A. In this position, the microneedle (15) is held within the apparatus without extending through the space (45). This is the configuration in which the apparatus is provided for use and applied to the skin of the subject.

[0143] The arm (20) is connected to a microneedle attachment block (70) that supports the microneedles. The attachment block (70) also includes a conduit (not shown) for carrying current from each of the microneedles (15) to one of several connection points (75) on the PCB (65). With this configuration, electrical signals can be transmitted to and / or from the microneedles embedded in the skin of the subject. For example, the apparatus can be configured as a sensor comprising microneedles configured to contact a biological fluid within the subject's body and detect an analyte therein. The biological fluid can be, but is not limited to, interstitial fluid, blood, or a mixture thereof. Electrical signals from the microneedles are transmitted to the PCB for amplification, filtering, encoding, analysis, transmission, or other electrical or electronic processes.

[0144] In this embodiment, the PCB serves a dual function as a driving means for transporting the electronic devices of the apparatus and also for moving the microneedles from an internal position to an external position within the apparatus. The PCB material has been found to be well - suited for providing a preferably limited range of movement for the arms of the present apparatus. This configuration reduces the number of components within the apparatus.

[0145] The upper surface of the housing (25) exposes the actuating surface of a button (215) that can be depressed by the user's finger. The button (215) is biased upward (as shown in the figure) by a spring or by being integrally formed with the housing (25) material. In the latter form of biasing, the button (215) is integral with the housing material and can be attached to an arm that biases the button (215) such that its upper surface is in the same plane as the housing (25).

[0146] The lower part (not visible) of the button (215) is located on the upper surface of the arm (20), the upper surface of which is the back of the PCB (65). Depressing the button (215) biases the arm (20) downward to release it from the protrusion (55) and assume a second position. In the second position, it will be understood that the microneedles extend through the spaces (45) respectively and are embedded in the underlying skin (e.g., the epidermis, dermis, or subcutaneous tissue of the subject).

[0147] The natural biasing of the PCB (65) material towards the second position is strong enough to keep the arm (20) in the second position without the need for means to lock the arm in the second position. Thus, the microneedles (15) can be left embedded in the subject's skin for an extended period.

[0148] In an alternative embodiment, the arm (20) has a curved configuration when in the second position and is naturally biased away from the second position. In another embodiment, the biasing of the arm (20) towards the second position is not strong enough to prevent movement away from the second position. In such embodiments (and other embodiments), a locking mechanism may be provided to prevent movement of the arm away from the second position so that the microneedle (15) does not retract into the device and remains embedded in the skin. A suitable locking mechanism is the latch mechanism disclosed in connection with other embodiments herein. Other locking mechanisms will be apparent to those of ordinary skill in the art having the benefit of this disclosure.

[0149] The housing (25) has opposing recesses (80) to facilitate gripping between the user's thumb and second finger and to hold the device against the skin surface. The user's first finger can freely activate the button (215) to embed the microneedle (15) into the underlying skin.

[0150] The skin contact surface (35) may have a dermatologically acceptable adhesive layer (not shown) applied thereto to maintain the device in place on the subject's skin for an extended period of time. The adhesive layer can cover a portion or substantially all of the skin contact surface (35). As described for other embodiments of the device herein, a manually releasable flexible layer may cover the adhesive until the device is applied to the skin.

[0151] Next, referring to FIGS. 4, 5A, 5B, 6, and 7, a preferred device is shown that is generally configured and operable in accordance with the embodiment of FIG. 2B.

[0152] This embodiment has an upper housing portion (25) and a skin contact portion (30). A removable flexible layer (90) that can be grasped via a tab (95) is provided, and upon its removal, a dermatologically acceptable adhesive is exposed on the skin contact surface (35). As described above, the adhesive is intended to hold the device on the skin of the subject for an extended period of time. The flexible layer (90) functions to prevent curing or drying of the adhesive and to prevent contamination of the adhesive layer prior to use and / or premature adhesion of the adhesive to the packaging or other surfaces. In a particularly preferred embodiment, in addition to covering the adhesive layer, the flexible layer (90) extends over the space (45) to prevent contamination of the microneedles (15) and to help prevent inadvertent needle stick injuries to the user.

[0153] The device may have a holding portion that functions to hold the device on the skin such that the protruding portion remains in contact with the biological fluid of the subject. The holding portion may be dedicated to that function or may serve another function.

[0154] In many situations, a holding portion that is or includes a dermatologically acceptable adhesive would be useful. The adhesive can simplify application of the device by the user and often requires only removal of a protective backsheet to expose the adhesive, after which the exposed adhesive is brought into contact with the skin. This method of application is similar to applying a bandage and is thus a process already familiar to the user.

[0155] As an alternative to the use of an adhesive, the holding portion may be any mechanical means for maintaining the device at the required position on the skin. For example, the device may comprise a dedicated strap that engages around a limb that can be adjusted to maintain the device firmly applied to the subject. Alternatively, the device may be incorporated into a wearable item such as a glove or shirt, or a jewelry item such as a ring that functions to hold the device in a predetermined position. The device may be configured to engage with a separate wearable item (e.g., by complementary hook and loop means), or the wearable item may be integral with it.

[0156] In some embodiments, the device is held simply by supporting a wearable item against the housing. For example, the holding portion may be a snug-fitting elastic glove that is worn over the device.

[0157] In some embodiments, the holding portion is any surface or part of the device that contacts the subject's skin, and the features of the subject are at least partially responsible for maintaining the device in place on the subject. For example, the device may be configured to be held between two parts of the body that are normally in proximity, or within an existing anatomical structure. The device may be shaped and / or dimensioned to be held between the toes, in the buttocks, groin, mouth, nostrils, ear canal, or navel.

[0158] In other embodiments, the device housing is shaped and / or dimensioned to fit snugly over, for example, a finger, toe, or ear. The device housing may be elastically deformable and may be composed of, for example, a rubberized material and configured to be stretched over any anatomical part (such as a finger).

[0159] Each of the foregoing embodiments is considered to be a holding portion in the context of the present invention.

[0160] The device further comprises a release member (100) having a gripping portion (105) and a wedge portion (110), the function of which will be described in more detail below. The release means (such as the release member (100)) may be involved in the power regulator of the device and then power on the device when applied to the subject.

[0161] Here, looking at the exploded views of the components in FIGS. 5A and 5B, it is immediately apparent that they are similar to the components in the previous figures.

[0162] In this embodiment, the motive power for moving the arm (205), thereby pushing 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 by means of a hinge configuration.

[0163] The hinge configuration is provided via opposing lugs (115) extending from the skin contact portion (30), each lug having an opening. The arm (205) has opposing laterally extending disks (120), each disk seating in the opening of the lug (115). It is clear that the arm (205) can hinge relative to the skin contact portion (30) to enable movement from a first position to a second position.

[0164] The arm (205) is presented to the user with 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 removing the release member (100), the wedge portion is inserted between the skin contact portion (30) and the arm (205), thereby holding the microneedle within the device.

[0165] When attempting to apply the device to the skin of the subject, the user pulls on the tab (95) to remove the flexible layer (90) and expose the adhesive layer on the skin contact surface (35). The device is then applied to the skin and the adhesive holds it in place for an extended period of time.

[0166] When the device is applied to the skin, the user grips the gripping portion (105) and pulls it leftward (as shown in the figure) to completely remove the release member (100). The release member (100) has no further function and is discarded at this point. By removing the release member (100), the arm (205) is released from the first position and is allowed to move (under the downward force applied by the user) to a second position where 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 through the space (45) into the underlying skin.

[0167] As will be appreciated, the release member (100) can be configured to prevent the upper housing (25) of the device from closing against the skin contact portion (30) when not intended by the user. The release member (100) is inserted or juxtaposed between the upper housing (25) and the skin contact portion (30) and prevents the closing of the upper housing (25) towards the skin contact portion (30) sufficient to allow the tip of the microneedle (i.e., the protruding portion) to protrude from the base of the hole in the skin contact portion (30). Preventing the closing also prevents the movement of the arm (205) from the first position to the second position. Thus, when the release member (100) is in a predetermined position, the tip of the microneedle cannot be inadvertently accessed in a manner that would cause contamination or damage to the microneedle. 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 target skin and then removes the release member (100) before pressing the upper housing (25) to insert the microneedles into the skin.

[0168] Before removal by the user, the release member (100) can be held in place by any one of a variety of features. In one example, the release member (100) includes protrusions that fit into recesses in the upper housing (25), the skin contact portion (30), or both the upper housing (25) and the skin contact portion (30) to assist in holding it 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 either the upper housing (25) or the skin contact portion (30) assists in holding it in place until it is intentionally removed. In yet another example, magnetic forces can be used to assist in holding 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 disposed 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 available electronic circuit and converting from a sleep mode to an active mode. The above are examples of possible ways to assist in holding the release member (100) in place before intentional removal, which can be used alone or in combination, and it should be understood that other methods known in the art can also be used alone or in combination with the given examples.

[0169] 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) that extends downwardly towards the skin contact portion (30). The release member (100) includes a groove that allows the release member (100) to slide through the locking element when the release member (100) is pulled out of the device, while keeping the surface of the release member (100) facing the upper surface of the skin contact portion (30) continuous. In use, the release member (100) according to this preferred embodiment is removed and held by the user before pressing the upper housing (25) to insert the microneedle into the subject's skin. After the device is removed from the subject after use, the user is instructed to adhere the release member (100) to the adhesive layer on the lower surface of the skin contact portion (30) to cover the protruding microneedle. In another example of this embodiment, the release member (100) remains attached to the device even after being pulled out by the user, and is then flexibly attached to the device so that it can be repositioned to cover the protruding microneedle after the device is removed from the subject after use. In yet another example of this embodiment, the release member (100) and the upper housing (25) are designed such that after the release member (100) is removed, they can engage with the upper housing (25) slidably or in some other way, and the release member (100) is intended to be stored during use of the device and removed for use as a cover element after the device is removed from the subject.

[0170] In some embodiments, the device is configured to facilitate the user when removing the device from the subject. As will be understood, the use of an adhesive layer may make it difficult to remove the device from the skin. Examples of such configurations include leaving a portion of the skin contact surface (35) uncoated with adhesive so that there is a gap between the subject's skin and the surface (35), and the user uses this gap as a lever point to help pull the device away from the skin by breaking the bond of the adhesive. In another example, a lever mechanism that is not disposed on the skin contact surface is incorporated to allow a higher gap than the gap formed by the absence of adhesive on a portion of the skin contact surface. In yet another example, a tab extending beyond at least one end of the skin contact portion (30) and attached to the adhesive layer can be incorporated, in which case the user extends and yields the adhesive layer and pulls the tab with sufficient force to peel the adhesive from the skin contact surface (35) and the skin.

[0171] In some embodiments of the present invention, the device is designed such that the release member (100) is locked in its position before 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 pulled out. In an example of this embodiment, the release member (100), and at least one of the upper housing (25) and the skin contact portion (30), have features that engage lockably when the upper housing (25) is not being pushed. When the upper housing (25) is pushed down, the features of at least one of the upper housing (25) and the skin contact portion (30) are distorted, thereby disengaging the engagement of the release member (100) and allowing it to be pulled out.

[0172] In yet 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 such that it does not substantially bend when subjected to a closing force that may be present in the user's hand during manufacturing, storage, and prior to application to the subject, but is sufficiently flexible to bend when the user intentionally applies a closing force to the device when applied to the subject's skin. When bent in this way, the release member (100) bends, allowing the upper housing (25) to close towards 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, features such as those labeled (220) in FIGS. 5A, 5B, and 7 form the release member (100).

[0173] Each space (45) of the device is sized such that the microneedles can clearly extend therethrough, and at least the tapered portion of the microneedles does not affect the sides of the holes during insertion. In some embodiments, the holes can be of a sufficient cross-section such that no portion of the microneedles contacts the sides of the space during insertion. In other embodiments, at least a portion of the holes along their length have a cross-section such that a portion of the length of the microneedles contacts the sides of the holes during insertion. According to this embodiment, the holes function to help support a portion of the length of the microneedles to help prevent the microneedles from bending when inserted.

[0174] In some embodiments of the device, the skin contact portion (30) has an additional space or recess configured to receive a protrusion on the release member to help hold the release member until removed by the user. Further, or alternatively, the skin contact portion (30) includes a protrusion designed to be received within a recess of the release member to help hold the release member in place until intentional removal by the user.

[0175] The embodiments shown in FIGS. 4, 5A, 5B, 6, and 7 have a locking portion in the form of a latch (220) that permanently locks the arm (205) in a second position that prevents the arm (205) from hinging. In the illustrated embodiment, the latch (220) can flex in response to movement of the arm (205) toward 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. It is a simple single member that can.

[0176] The locking portion may act on another component of the device rather than on the arm (205), and that component locks the arm in place. For example, the locking portion may act on the upper housing (25), and the upper housing (25) holds the arm (205) in the second position. In a further alternative, the locking portion may act on the PCB (65), and the PCB (65) holds the arm (205) in the second position.

[0177] In other embodiments, the locking portion has a recess into which a protrusion on the upper housing (25) is inserted to lock the upper housing (25) in the closed position (i.e., the state where the arm (205) is in the second position). In one embodiment, the locking portion has a flexible element designed to allow the locking portion to move when struck by the upper housing (25), such that the housing (25) is allowed to close relative to the skin contact portion (30), and thereby, when the upper housing (25) is closed, the locking portion moves to lock the upper housing (25) in the closed position. In one embodiment, the device has a protrusion on the upper housing (25) designed to be inserted into the recess of the locking portion, the protrusion having a flexible element that allows the protrusion to move, allowing the upper housing (25) to close relative to the skin contact portion (30), and after the housing (25) is closed relative to the skin contact portion (30), the protrusion moves and is inserted into the recess of the locking portion to lock the upper housing (25) in the closed position. The flexible element may include a shaft that is deformable enough to allow the upper housing (25) to close without yielding of the shaft, such that the flexible element attempts to return to its original position after the upper housing (25) is closed. Although less preferred, in a functional embodiment nonetheless, the flexible element includes a coil spring.

[0178] The flexible element of the locking portion can be manufactured from any suitable material having the required rigidity and yield point. Examples of suitable materials include amorphous plastics, crystalline plastics, spring steel, unsprung steel, stainless steel, or other materials known to those skilled in the art having suitable mechanical properties.

[0179] 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.

[0180] 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 such 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 sets the force required to close the device (thereby causing the arm to assume a second position), and that force is used to ensure that it is sufficient to insert the microneedles into their intended positions embedded in the skin.

[0181] In other embodiments, the locking portion has at least one adhesive region located on at least one of the lower surface of the upper housing (25) and the upper surface of the skin contact surface (35). When the device is closed, the one or more adhesive regions adhere the upper housing (25) to the skin contact portion (30) and lock the device in the closed position.

[0182] In another embodiment of the present invention, the locking portion can take three different stable states. In the first state, the locking portion is in a disengaged configuration before the upper housing (25) is pushed downward toward the skin contact portion (30) to close the device. In the second state, the locking portion is in the first engagement position. When the locking portion is in the first engagement position, it serves to lock the microneedles (15) in the implanted position within the skin (i.e., when 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 open position (i.e., with the arm (205) in the first position) with the microneedles retracted into the device to improve the likelihood of needle stick injuries due to the microneedles protruding after use of the device. In an example of this embodiment, the locking portion has a user engagement portion that can be gripped by the user or otherwise engaged, for example, by engaging a claw under a protruding overhang 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 it in a predetermined position as in the other embodiments disclosed herein. If it is desired to remove the device from the subject, the user engages the locking portion and deflects it in a first direction to unlock the upper housing (25) from the skin contact portion (25), and then deflects the locking portion in a second direction to lock the device in the open position (i.e., with the arm in the first position) where the microneedles are retracted. 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, it is moved toward the body of the device. When sufficiently deflected in the second direction, the locking portion is designed to stably engage in a recess, for example, to prevent unintentional closure of the device.

[0183] In some embodiments of the present invention, the downward force on the microneedles when inserted into the skin is provided via a flexible element of a locking portion that applies a downward force when the device is locked in the closed position (i.e., with the movable arm in the second position). In some embodiments, effective locking of the movable arm in the second position is provided by a dedicated spring or other suitable biasing means. In other embodiments, the spring or other biasing means is not dedicated to the locking function and can also act, for example, as a 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 behind the microneedle and, when the device is closed, the spring is distorted or compressed to apply a downward force on the microneedle when the device is in the closed position.

[0184] Although not an essential feature of the present invention, a PCB (65) is required for many applications where the microneedles are intended to conduct current to, from, or through the skin. In this 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 will of course typically include a power source, typically a button cell battery.

[0185] The embodiment shown in FIG. 3A further includes a light emitting diode (LED) (120) visible to the user. One function of the LED (120) may be to confirm to the user and / or subject that the microneedles are properly embedded in the skin upon application and maintain that state for extended wear.

[0186] The LED makes an electrical connection to the PCB (65), which in turn makes an electrical connection to the microneedles (15). The proper embedding of the microneedles can be determined by referring to any one of the current flow, resistance to current, or impedance between two microneedles.

[0187] Alternatively, the proper embedding of a single microneedle can be determined by referring to any one of the current flow, resistance to current, or impedance between the single microneedle and other electrical contacts 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, which cooperates with at least one of the microneedles, completes the electrical circuit when the microneedle is inserted into the skin. The completion of this circuit is used to indicate the correct insertion of the microneedle.

[0188] The electronic circuitry involved can be simple, and in any of its examples, it is a biological fluid of the skin, such as interstitial fluid (which is naturally conductive), that acts to complete the circuit including the LED. Assume that proper embedding is indicated by simple contact between the microneedle and the biological fluid. The LED is lit where the microneedle contacts the biological fluid (or vice versa), thereby providing a visual indication of correct embedding.

[0189] To provide a higher level of assurance of correct micro-needle implantation, a more sophisticated electronic configuration may be required. For example, it may be necessary to consider whether the micro-needle of minimum length is implanted, thereby providing assurance of the insertion of the micro-needle to a specific minimum depth. The device may have electronic means for measuring a quantity of a parameter such as a current flow, and a higher current flow indicates a more complete implantation of the micro-needle. Program instructions executed by a processor mounted on the device or a related processor in another way may use a parameter such as a current flow (which may be combined with other physiological or environmental parameters) as an input to provide an indication of the degree of micro-needle implantation.

[0190] 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 slightly exceeds the minimum operating voltage to give the subject time to access a replacement battery (or a replacement device if the battery is not user-serviceable) before the device becomes inoperable.

[0191] In other embodiments, the LED may generate an output display of the data connection state. For example, the LED may alternately flash red and green lights to warn of an interruption in the wireless data connection with a remote device such as a smartphone. The smartphone may be responsible for processing the sensor output and warning the subject by audible output when a threshold (such as glucose concentration) is breached. In such embodiments, the LED and the device network module may be connected to a microprocessor, which monitors the connection state of the module and causes an output to be generated for the LED when the connection is established and / or lost. The application software on the smartphone may be configured to warn the user of the loss of the data connection, but the smartphone may lose power (e.g., run out of charge), in which case the only means of warning the subject is via the device itself.

[0192] An output function similar to that of the LED may be provided by a buzzer or a small speaker for providing audible output that can be understood by the subject. The output may be, for example, a tone, a series of tones, or a synthesized voice.

[0193] Next, reference is made to an alternative embodiment of the device shown in FIG. 9, which is a modified version of the embodiment shown in FIGS. 4 to 8. The embodiment of FIG. 8 includes a temperature sensor (300) that extends through a space (305) of a skin contact portion (30) so as to contact the surface of the subject's skin during operation. The temperature sensor (300) may be, for example, a thermocouple or a thermistor operably connected to a microprocessor on a PCB (65). The temperature sensor may be in direct contact with the skin or may be separated from the skin via a thermally conductive material.

[0194] The temperature sensor may be disposed within a pocket or other formation sized to receive the temperature sensor. The pocket may be made of a thin sheet-like material of plastic such as thermally conductive plastic having a metal or other filler that facilitates the transfer of thermal energy from the underlying skin to the temperature sensor. The temperature sensor may be surrounded by a thermally conductive paste to facilitate the transfer of thermal energy from the pocket wall to the temperature sensor.

[0195] The floor of the pocket can extend outward from the device such that when the device is applied, the floor of the pocket is gently pressed onto 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 onto the skin surface too strongly can push blood out of the skin capillaries, thereby artificially cooling the skin surface.

[0196] Preferably, only the floor of the pocket is manufactured from a thermally conductive material and the remainder is manufactured from a low thermal conductivity material. With that configuration, thermal energy from the skin is not sent away from the temperature sensor.

[0197] An insulating material can form the ceiling of the pocket such that thermal energy is retained around the temperature sensor and not lost to the internal cavity of the housing.

[0198] The pocket can have a space extending through the floor such that the temperature sensor can be in direct contact with the skin surface. Given that it is not required for thermal energy to pass through an intervening material, a temperature close to the actual skin temperature is expected.

[0199] In a further variant, the temperature sensor can be an infrared sensor module, in which case at least the material of the pocket floor must not substantially interfere with its operation. It is contemplated that a space can be formed in the floor such that the infrared sensor module is directly exposed to the skin surface to enable accurate reading of the skin temperature.

[0200] The signal output from the temperature sensor (300) can be used in calculations performed by a microprocessor (or remote microprocessor) to more accurately determine the concentration of the target analyte. For example, the microprocessor can access a stored calibration curve range, each curve having been performed at a given temperature. Based on the output of the temperature sensor (300), an appropriate calibration curve can be selected and thus a more accurate analyte concentration determined.

[0201] The embodiment of FIG. 9 has a release member (100) having a pair of protrusions (a first protrusion labeled 310, the second protrusion of the paired protrusions being hidden by the first protrusion). The protrusion (310) extends downward through the space (315) of the skin contact portion (30). The function of the protrusion (310) is to prevent the lateral movement of the release member (100) until the lower surface of the skin contact portion (30) is pressed against the skin. The pressing operation against the skin vertically escapes the protrusion (310) from the space (315) so as to enable the release member (100) to be laterally pulled away by the subject. This mechanism prevents the release member (100) from being inadvertently removed before the device is properly applied to the skin surface. Without such a mechanism, the microneedles (15) may be prematurely extended through the space (45), may be contaminated by contact with air or objects, or may be physically damaged, for example, by being caught on clothing.

[0202] Some embodiments of the present device may require that the upper region of the microneedles be electrically insulated to avoid the formation of a conduction path between the microneedles by the wet surface of the skin (different from the biological fluid thereunder).

[0203] As another means of controlling moisture, an absorbent material can be disposed on the micro-needle attachment portion and proximal to the tip of the micro-needle. In embodiments of the device for sensing applications, the material is configured to absorb any excess fluid that may be generated by the insertion of the micro-needles into the skin in order to improve the subject's experience and to mitigate problems that may be caused by fluid contact with other parts of the device such as electronic circuitry or electrical contacts. In embodiments of the device such as for fluid extraction applications, the material acts as a wicking agent to transport fluid from the micro-needle site to the required final site on or external to 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 has holes through which the micro-needles pass, the holes being large enough to prevent the absorbent material from contacting the micro-needles during the insertion process of the micro-needles, but small enough in dimension to allow excess fluid exuding from the access penetration points formed by the micro-needles to contact and be absorbed by the material. In other embodiments such as when 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 with the wicking action. In embodiments where the sheet has no holes, the micro-needles form holes as they pass through the sheet as part of the insertion process.

[0204] The device can be configured and / or used for use in any suitable application where the micro-needles need to be embedded in the subject's skin for an extended period of time.

[0205] 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 upon 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.

[0206] When the micro-needle functions as an electrode to detect an analyte present in a layer of skin, the device may have circuitry and components for electrically exciting the electrode and receiving, measuring, and processing the electrical signal resulting from the electrical excitation. According to this embodiment, the micro-needle may have a tip, a shaft, and a base, and the electrical signal is generated at an electrode that is coated on the surface of the micro-needle or integrated into the micro-needle, 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 proximal to the tip of the micro-needle, on at least a portion of the shaft of the micro-needle and not proximal to the tip of the micro-needle, or on both proximal to the tip of the micro-needle and on at least a portion of the shaft of the micro-needle.

[0207] The microneedles can be connected to an electronic circuit by various methods known in the art, such as soldering, wire wrapping, or spring pins. In one embodiment, the microneedles are attached to pass through a plate or block of a dielectric material, and the connection portion of the microneedles is disposed on the surface of the plate or block distal to the tip of the microneedles. Zebra strip connections can be used to connect the microneedles to an electronic circuit, facilitating a robust connection without the need to accurately align the zebra connector with the microneedle end in at least one dimension.

[0208] Further potential uses are the delivery of an electric current to the skin for the purpose of muscle stimulation, or the stimulation or inhibition of a biological process of a subject. Similarly, the device can be used to detect an electric current in the skin of a subject, for example, to detect nerve conductance.

[0209] In any of the above uses, the microneedles can be solid or hollow, as required or desired.

[0210] The length of the microneedles can be selected according to a particular use. Typically, the microneedles are required to extend at least under the stratum corneum. The depth of the stratum corneum varies by location; for example, the layer is relatively thick on the sole of the foot and relatively thin on the back of the hand. Thus, the length of the microneedles extending beyond the housing can be adjusted according to the intended site of application.

[0211] In some cases, the microneedles may be required to extend well under the stratum corneum and into the underlying layer, the dermis, and even the hypodermis, including the subcutaneous tissue. Again, the length of the microneedles extending beyond the device can be set accordingly.

[0212] Further explanation is provided in connection with the power regulator of the device. The device has electronic equipment configured to implement the functions of the device, and the electronic equipment is powered by a power regulator or with the assistance of a power regulator. The nature of the electronic equipment is of course determined by the functions of the device. The present invention is described herein mainly by referring to non-limiting examples of wearable electrochemistry aptamer-based (EAB) sensors, in which case the electronic equipment typically includes a microprocessor, and / or volatile electronic memory (such as RAM) and / or non-volatile electronic memory (such as ROM) and / or software instructions for the operation of the device and / or a wireless networking module (such as a Bluetooth® module). The device typically has a power source by a button cell.

[0213] In an exemplary EAB sensor, the micro-needles form the electrodes of the EAB sensor. One of the electrodes is a working electrode functionalized with an aptamer that can specifically bind to the analyte of interest. Similar devices include those that use needles or wires instead of micro-needles as electrodes. A square-wave potentiostat may be included in the electronic equipment of the device to acquire information from the working electrode. There may also be software for analyzing the current passing through the electrodes and attributing it to the analyte concentration.

[0214] In the context of a wearable micro-needle-based device, the device is typically applied to the skin such that the micro-needles penetrate into the subcutaneous tissue and thereby contact the interstitial fluid. In order to detect the analyte, the device must be fully powered so that its potential can be applied to the working electrode when required to acquire information. Since the device is provided to the user in a sleep mode (with very low power consumption) or a state where the electronic equipment is not fully powered, it is the user's responsibility to ensure that the device is powered on before applying it to the subject.

[0215] If the user fails to power on the device, the error may go unnoticed, and thus the device may remain unable to detect the analyte. In the absence of output from the device, there may be an incorrect assumption that the analyte has not been detected.

[0216] If the error is noticed, the user must attempt to power on the device while the microneedle is embedded in the subcutaneous tissue. For example, a mechanical switch may need to be manually actuated by the user, in which case the entire device may be moved, potentially leading to movement of the microneedle. Such movement can cause tissue damage or even removal of the microneedle.

[0217] In view of the capabilities of the device that can be performed in the absence of an intentional action by the user, the present invention avoids the need for the user to power on the device. The device of the present invention is configured to power on through operations related to preparing for use that are not normally associated with powering on the device, such as removing the device from the package, removing the guard of the device, opening the device, exposing any microneedles, etc. during the normal placement process. In the context of the present invention (with the aim of avoiding the need for the user to perform a dedicated power-on operation), the operations that occur during the normal placement process do not include dedicated power-on operations such as actuating an "on" switch.

[0218] According to the present invention, the device is not powered or remains in a low-power sleep mode until immediately before use, thereby extending the shelf life of the device without the attendant risk of the user neglecting to power on the device before use.

[0219] The device may use sensors configured to detect operations that occur during the normal placement process. The sensors may be components of the power regulator or may be operably connected to the power regulator. When the sensors detect the relevant operations, electrical signals may be communicated from the sensors to the power regulator. For example, the sensors may communicate operably with the device's processor, and the electrical signals from the device may cause the device to enter a startup routine, and in that process, fully power the device's electronics to enable the normal operation of the device. The sensors may output changes in resistance, capacitance, voltage, current, digital or analog signals, or several other electrical outputs or parameters.

[0220] In some embodiments, the power regulator is also a sensor. As an example of such an embodiment, a switch can perform both functions that an operation executed during the placement of the device closes the switch, the closing of the switch senses that operation, and further connects the power supply to the device's electronics, thereby also providing a power regulation function.

[0221] The placement of the device may require any number of operations to be performed. The first exemplary step in the placement of the device is removal from the packaging, and the last exemplary step is to apply the device and configure it to be operable. Such operations can be utilized to automatically power on the device.

[0222] As a first exemplary operation in the placement, the device may be removed from a light-shielding package, and the sensor is a light sensor that senses when the device is removed and exposed to ambient light.

[0223] Further operations may include separation of the device from a packaged item, a protective item, a guard (e.g., for covering a microneedle), or a blocking item (e.g., for maintaining the microneedle within the device until application of the device to a subject). The separation operation may trigger a Hall effect sensor. In one embodiment, the item separated from the device has a permanent magnet proximal to the sensor prior to separation, and removal of the item moves the magnet distal to the sensor, thereby changing the voltage output. In another embodiment, the item normally has a conductive portion that contacts two conductive portions on the device to close a low-resistance circuit, and separation of the item causes the circuit to open, leading to essentially infinite resistance being detectable within the circuit.

[0224] Further operations that may be performed during the placement of the device include movement of one part of the device relative to another part. For example, the device may be hinged and need to open and close for normal operation. If the device has a microneedle, the device may have a first portion with a microneedle extending therefrom and a second base portion that contacts the subject's skin and has an opening that allows passage of the microneedle. Prior to application of the device, the two parts are hinged open slightly and the microneedle is placed on the base portion. The base is applied to the subject's skin and the first portion is hinged downward so that the microneedle extends into the skin through the opening. The movement of the hinging operation may be sensed by a microswitch, a Hall effect sensor, a strain sensor, a pressure sensor, or any other type of sensor that one of ordinary skill in the art deems appropriate.

[0225] Some embodiments have a sensor configured to detect contact of the device with a subject, which is a further exemplary step in placement. For example, the sensor may be a thermal energy sensor such as a thermistor or a thermocouple configured to sense heat emitted by the subject. In another embodiment, a capacitance-based touch sensor may be used. In a further embodiment, a conductivity sensor that senses an increase in applied current when in contact with the skin may be used.

[0226] When the power regulator senses the operations performed during the normal placement process, the device transitions to a fully operational state. For example, the power regulator may trigger a software instruction routine that causes the processor to start full operation in a manner similar to when a personal computer transitions from sleep mode. In this regard, the device transitions to a state where more power is consumed. If the device has functionalized electrodes for detecting an analyte, the transition to the full operation mode may include applying a potential necessary for detecting the analyte to the electrodes.

[0227] In other embodiments, the power regulator directly controls the amount of power supplied to the device electronics, for example, by being disposed in an electrical circuit between the power source and the device electronics. In such embodiments, the power regulator may be a relay-like device that can separate or connect the device electronics from the power source, for example, in response to an input from a processor. When in the first state, the power regulator does not supply any power to the device electronics, unlike the sleep mode in which some current is drawn. When in the second state, the power regulator forms an electrical connection that allows current to flow from the power source to the device electronics, thereby powering on the entire device and enabling normal operation.

[0228] Referring to FIG. 10, the arm (205) of the device includes a pair of contacts (600a, 600b) (upper panel) that form an open electrical circuit. When the device is closed during the placement process to expose the micro-needles (not shown) (lower panel), the circuit is closed to a connector (605) within the base (30). Thus, when the closure of the device is sensed, the closed circuit thus formed connects a power source (not shown, such as an on-board battery) to the device electronics to power on the device for operational use. In that configuration, the combination of the contacts (600a, 600b) and the connector (605) provides both power regulation and sensing functions.

[0229] Alternatively, the closed circuit may trigger a processor (not shown) to return the device from sleep mode, and in that process, consume more power from the power supply. In that configuration, the combination of contacts (600a, 600b) and connector (605) provides a sensing function, and the processor is a component that actually adjusts the amount of power supplied to the device electronics.

[0230] The embodiment of FIG. 11 is a variation of the embodiment of FIG. 10, differing in that the connector is replaced by the skin (50) of interest. In the embodiment of FIG. 11, the contacts (600a, 600b) may form part of a conductivity sensor or a resistance sensor, and the signal therefrom is transmitted to a processor that adjusts the power supplied to the device electronics.

[0231] The embodiment of FIG. 12 is a variation of the embodiment of FIG. 2, differing in that the base (30) itself is conductive and thus functions as a connector.

[0232] The embodiment of FIG. 13 is a variation of the embodiment of FIG. 12, differing in that the arm (205) is not hinged to the base (30), but instead is held above the base (30) by a pair of protrusions (610). When placed, the arm (30) is pushed down (lower panel) to move downward within the base (30). The base (30) is conductive and closes the circuit between the contacts (600a, 600b). Typically, the lower surface of the connector (30) contacts the skin surface with the arm (30) in the upper position (upper panel) and is pushed down by the user to take the lower position (lower panel). The microneedles (not shown) enter the skin (not shown) through the openings in the base (30).

[0233] The embodiment of FIG. 14 includes an arm (205) hinge - connected to a base (30), and these two components are held in an open configuration (upper panel) by a protrusion (55) that acts to prevent downward movement of the arm (205). The protrusion (55) includes a space that allows a microneedle (not shown) to extend therethrough. The protrusion (55) is removed by the user during the placement process, allowing the arm (205) to swing downward so as to push the microneedle through the base (30) into the underlying skin (not shown). In this embodiment, the removal of the protrusion (55) is sensed by a Hall - effect sensor (620) disposed on the arm (205). The protrusion (55) has a magnet (625), and its movement (bottom panel) is sensed by the Hall - effect sensor (620). The output of the Hall - effect sensor (620) is sent to a processor (not shown), and the processor adjusts the power supplied to the electronics of the device.

[0234] FIG. 15 shows an embodiment that is a variation of that depicted in FIG. 14, the difference being that the magnet (625) is disposed within a packaging insert (630). The device is provided to the user as shown on the upper panel, and the user removes the device from the packaging insert (630) during the placement process as shown on the lower panel. The removal of the packaging insert (630) moves the magnet (625) relative to the Hall - effect sensor (620).

[0235] FIG. 16 shows an embodiment that is a variation of that depicted in FIG. 15, the difference being that the magnet (625) is disposed within a removable adhesive liner (635). In this embodiment, the lower surface of the base (30) is coated with an adhesive configured to adhere the device to the skin of the subject. The adhesive is covered by a liner (635) that is removed by the user during the placement process to expose the adhesive. When the adhesive is exposed, the device is powered on by a power regulator immediately before being applied to the subject.

[0236] FIG. 17 shows an embodiment that is a variation of what is depicted in FIG. 13, the difference being that the switch (630) is attached to the arm (205) and the switch (630) replaces the contact and the connector. The switch (630) is open (upper panel) when the arm (205) is in the upper position, but closes by mechanical contact with the non-conductive base (30).

[0237] FIG. 18 shows an embodiment that is a variation of what is depicted in FIG. 10, differing in that the switch (630) is closed by mechanical contact with the lower skin (50).

[0238] One skilled in the art will also appreciate the potential need to set the length of the microneedle according to the intended subject. For example, to achieve contact with the subcutaneous tissue of a neonatal subject, generally relatively short microneedles are required, while for an adult subject at the same site, longer microneedles will likely be required.

[0239] In some applications, it may be desirable for one microneedle to penetrate deeper into the skin compared to another microneedle. Thus, the two microneedles can terminate at different distances from the skin surface or at different distances from the microneedle attachment portion. In some embodiments, the two microneedles are of different lengths. In other embodiments, the microneedles are of the same length and the attachment portion is configured to axially displace one microneedle relative to the other. For example, the attachment portion may be a multilayer having a first electrode extending from a first level and a second electrode extending from a second level.

[0240] In a typical application, the microneedle can extend outward from the device by a distance between about 10 μm and about 5000 μm. In many applications, a distance between about 500 μm and about 4000 μm will be useful.

[0241] Those skilled in the art will understand that the invention described herein is susceptible to further variations and modifications other than those specifically described herein.

[0242] For example, the movable arm can be moved by the user pushing or pressing on the flexible portion of the device housing, by actuating a rotary lever, or by sliding an element along an incline so as to bias the arm downward.

[0243] The skin contact portion of the device is depicted as being strictly planar at its lower surface (skin contact surface), but in some embodiments, it can be curved to conform to the surface of a body part such as a finger, wrist, heel, or ear. The skin contact portion can have a degree of flexibility (in at least one direction) to conform to the surface of the body part.

[0244] The space through which the microneedles extend is generally shown as an opening, but other types of spaces are also contemplated. In some embodiments, the space is not an opening, and one such embodiment has microneedles extending through the space around the skin contact portion.

[0245] It is understood that the present invention includes all of the foregoing variations and modifications, and in fact further variations and modifications, that are within the spirit and scope of the present invention.

[0246] 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 allowable by law.

Claims

1. A device for bringing one or more protrusions into contact with the target skin: One or more protrusions, each configured to penetrate the skin; A skin contact portion that defines a skin contact surface and one or more spaces that allow the one or more protruding portions to extend through; A movable portion configured to move one or more of the aforementioned protruding portions from a first position behind the skin contact surface to a second position protruding from the skin contact surface; An electronic device configured to perform the functions of the device having a power supply; Enclosures surrounding the electronic equipment and the power supply; and Power regulator; The power regulator is operable to take a first state in which the electronic device consumes no power or a non-operating amount of power, and a second state in which the electronic device consumes an operating amount of power, and the device is configured such that the power regulator can be transitioned from the first state to the second state without a dedicated power-on operation performed by the user during the normal setup of the device. Device.

2. It has a retaining portion configured to maintain the skin contact surface in contact with the skin when in use, The apparatus according to claim 1.

3. The movable part is configured to move from the first position to the second position in a nonlinear path. The apparatus according to claim 1.

4. The aforementioned nonlinear path is a roughly arc-shaped path. The apparatus according to claim 3.

5. The movable part has a connecting end and a free end. The apparatus according to claim 3.

6. The free end travels a longer distance than the connected end. The apparatus according to claim 5.

7. The nonlinear path is described by referring to the free end. The apparatus according to claim 5.

8. The aforementioned nonlinear paths are approximately 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, or less than 3 mm. The apparatus according to claim 3.

9. The degrees of the aforementioned arc are approximately 45°, 40°, 35°, 30°, 25°, 20°, 15°, 14°, 13°, 12°, 11°, 10°, 9°, 8°, 7°, 6°, or less than 5°. The apparatus according to claim 4.

10. The movable part has a pivoting part, a hinged part, a bending part, or an attachment part. The apparatus according to claim 1.

11. The aforementioned movable part is related to the mounting part, The apparatus according to claim 1.

12. During use, the mounting portion remains stationary, and the movable portion is movable relative to the mounting portion. The apparatus according to claim 11.

13. The mounting portion includes a portion that allows the movable portion to rotate, hinge, bend, or attach. The apparatus according to claim 11.

14. The aforementioned mounting portion is fixed to the skin contact surface at a distance, The apparatus according to claim 11.

15. The mounting portion can be spaced approximately 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, or less than 2 mm from the skin contact surface. The apparatus according to claim 11.

16. The aforementioned mounting portion is located in a direction generally laterally to the aforementioned movable portion. The apparatus according to claim 11.

17. A user-operable release portion further comprises a release portion configured to hold the movable portion in the first position until the user operates the release portion, and when the user operates, the movable portion is released and made capable of moving to the second position. The apparatus according to claim 1.

18. The system further includes a locking portion configured to lock the movable portion when it is in the second position, The apparatus according to claim 1.

19. The movement of the movable part from the first position to the second position is configured to require a driving force generated from inside and / or outside the device. The apparatus according to claim 1.

20. The power source within the device is due to a spring, an elastically deformable member, a shape memory member, or other biasing means; the power source outside the device is due to the user. The apparatus according to claim 19.

21. It lacks an internal power generator configured to move the movable part from the first position to the second position. The apparatus according to claim 1.

22. The retaining portion is a dermatologically acceptable composition disposed on or around the skin contact surface, or contains the dermatologically acceptable composition. The apparatus according to claim 2.

23. The dermatologically acceptable composition is an adhesive or a functional equivalent thereof. The apparatus according to claim 22.

24. The holding portion is configured to mechanically hold the skin contact surface in contact with the skin. The apparatus according to claim 2.

25. The retaining part is selected from one or more of the following: strap, band, belt, clamp, grip, tie, clasp, sleeve, stocking, sock, glove, cap, hat, pants, tank top, shirt, bra, top, trousers, scarf, ring, glasses, and choker. The apparatus according to claim 24.

26. The one or more of the aforementioned protruding portions are mechanically connected directly or indirectly to the movable portion. The apparatus according to claim 1.

27. The one or more protruding portions are wires, needles, and / or microneedles. The apparatus according to claim 1.

28. The one or more protruding portions form an array. The apparatus according to claim 26.

29. The one or more protruding portions are of sufficient length to be able to contact the epidermis, dermis, or subcutaneous tissue of the target. The apparatus according to claim 1.

30. The one or more protruding portions are configured to function, during use, to conduct electric current into, from, or through the skin; to transmit sound waves into, from, or through the skin; to guide light into, from, or through the skin; to transmit heat into, from, or through the skin; to sample fluid or tissue from the skin; to deliver a biologically active substance to the skin; or to introduce an analyte-sensing substance to the skin. The apparatus according to claim 1.

31. Each of the one or more protruding portions is conductive, and the device further comprises a circuit having an audio, visual, or tactile indicator, the circuit being configured to activate the indicator when the one or more protruding portions are in contact with a conductive fluid naturally present on the skin. The apparatus according to claim 1.

32. The circuit includes at least two protruding portions, and the circuit is configured such that the at least two protruding portions come into contact with a conductive fluid naturally present on the skin in order to activate the indicator. The apparatus according to claim 31.

33. The circuit includes a protruding portion and at least one conductive pad positioned against the skin, and the circuit is configured to be completed by the protruding portion and the pad being electrically connected to a conductive fluid naturally present in the skin in order to activate the indicator. The apparatus according to claim 31.

34. A housing having dimensions such that, when the device is applied to the skin, the movable part is in the second position, and any portion of each of the one or more protruding parts that protrude from the skin contact surface is embedded in the skin, the housing extends over the skin by approximately 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm or less for most or substantially all of its parts. The apparatus according to claim 1.

35. Configured to be used for a period exceeding approximately 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, 48 ​​hours, 60 hours, 72 hours, 84 hours, or 96 hours. The apparatus according to claim 1.

36. The one or more protruding portions are configured to be inseparable from the device or to be inseparable without the assistance of a tool. The apparatus according to claim 1.

37. The movable part and the mounting part are integrated. The apparatus according to claim 11.

38. The movable part and the mounting part are manufactured from an elastically deformable material. The apparatus according to claim 37.

39. The movable part and the mounting part are an integral part of the circuit board of the device. The apparatus according to claim 37.

40. The movable portion is biased toward the second position and held in the first position by the user-operable release portion until the user-operable release portion is activated, and when the user-operable release portion is activated, the movable portion is released and made able to move to the second position. The apparatus according to claim 17.

41. The user-operable release portion is a protrusion configured to hold the movable portion in the first position, and a driving force provided by the user deforms the protrusion and / or the movable portion so that the movable portion is released from the protrusion and moves to the second position. The apparatus according to claim 17.

42. The movable part is hinged to the skin contact portion. The apparatus according to claim 1.

43. The hinge is positioned in or toward the peripheral region of the movable portion and the skin contact portion. The apparatus according to claim 42.

44. The release portion has 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 claim 17.

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

46. The member is substantially wedge-shaped, and the device has a hinge that associates the movable part with the skin contact part, the thin part of the wedge is positioned proximal to the hinge, and the thick part of the wedge is positioned distal to the hinge. The apparatus according to claim 44.

47. The aforementioned release portion is removable from the device and has a grip portion to facilitate manual removal. The apparatus according to claim 44.

48. A user-operable release portion is provided, which is configured to hold the movable portion in the first position until the user operates the release portion, and when the user operates the release portion, the movable portion is released and made able to move to the second position. The apparatus according to claim 1.

49. The release portion has 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 claim 48.

50. The member is removable by sliding it across the skin contact portion. The apparatus according to claim 49.

51. The member is substantially wedge-shaped, and the device has a hinge that associates the movable part with the skin contact part, the thin part of the wedge is positioned proximal to the hinge, and the thick part of the wedge is positioned distal to the hinge. The apparatus according to claim 49.

52. The aforementioned release portion is removable from the device and has a grip portion to facilitate manual removal. The apparatus according to claim 48.

53. The power regulator is transitioned from the first state to the second state by an operation performed by the user during the normal setup of the device, and the operation is not a dedicated power-on operation. The apparatus according to claim 1.

54. The aforementioned actions are selected from the group consisting of: opening the package containing the device, separating the device from the packaging item, separating the device from the protective item, separating the guard portion of the device from the device, separating the spacer portion from the device, separating the blocking portion from the device, exposing a part of the device, moving a first portion of the device relative to a second portion of the device, opening the device, closing the device, sliding the first portion of the device relative to a second portion of the device, moving the hinge portion of the device, bringing a part of the device into contact with a fluid, and bringing a part of the device into contact with an object. The apparatus according to claim 53.

55. The aforementioned power regulator is configured to sense the aforementioned operation. The apparatus according to claim 53.

56. The power regulator electrically communicates with the processor of the device, and when the power regulator transitions to the second state, an electrical signal is transmitted to the processor so that the electronic device consumes or is permitted to consume a certain amount of power. The apparatus according to claim 1.

57. The power regulator has a sensor configured to sense the operation or communicates electrically with the sensor. The apparatus according to claim 53.

58. The sensor or power regulator detects electric field, electromagnetic field, magnetic field, light, strain, direction, acceleration, motion, thermal energy, conductivity, electrical resistance, capacitance, contact with human skin, pressure, strain, tension, torsion, compression, or motion. The apparatus according to claim 57.

59. The sensor or power regulator has a Hall effect sensor or another type of magnetic field sensor. The apparatus according to claim 57.

60. The sensor or the power regulator has an electrical switch. The apparatus according to claim 57.

61. The electrical switch has two spaced-apart electrical contacts that are present to the environment surrounding the device enclosure; and a movable conductive part that can contact both of the two separate electrical contacts to close the switch, the movement of which the movable conductive part opens and closes the switch. The apparatus according to claim 60.

62. The aforementioned electrical switch is located inside the device enclosure. The apparatus according to claim 60.

63. The power regulator and / or the sensor are substantially impermeable to fluid or vapor. The apparatus according to claim 57.

64. The device enclosure includes a flexible portion from which the power regulator can be operated. The apparatus according to claim 1.

65. The aforementioned flexible portion is substantially impermeable to fluid or vapor. The apparatus according to claim 64.

66. The flexible portion forms an interface with the main part of the apparatus enclosure, which is substantially impermeable to fluid or vapor. The apparatus according to claim 65.

67. The power regulator lacks an actuator that requires dedicated human operation to transition from the first state to the second state. The apparatus according to claim 1.

68. It has a working electrode configured to come into contact with a biological fluid, either intracellularly or extracellularly, and to detect an analyte within it. The apparatus according to claim 1.

69. The working electrode is a wire, a needle, or a microneedle. The apparatus according to claim 68.

70. A method for arranging a device, comprising providing the device according to any one of claims 1 to 69, and transitioning the power regulator from the first state to the second state in response to an operation performed by a user during the normal arrangement of the device.

71. The aforementioned actions are selected from the group consisting of: opening the package containing the device, separating the device from the packaging item, separating the device from the protective item, separating the guard portion of the device from the device, separating the spacer portion from the device, separating the blocking portion from the device, exposing a part of the device, moving a first portion of the device relative to a second portion of the device, opening the device, closing the device, sliding the first portion of the device relative to a second portion of the device, moving the hinge portion of the device, bringing a part of the device into contact with a fluid, and bringing a part of the device into contact with an object. The method according to claim 70.

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