Device for controlling needle penetration into skin

Abstract

An electrochemical sensing device for piercing a needle electrode into the skin of a patient to contact a biological fluid or tissue of the patient and to detect a target analyte. The device has a movable portion pushing the needle electrode into the skin of the patient and means for controlling the movement of the needle electrode. When the sensing device is actuated, the needle electrode is irreversibly pushed into the skin in real time.

Description

Technical Field

[0001] The present invention is generally directed to a device for introducing a needle into a patient's skin in a controlled manner and for holding the needle in place. The device is configured to be simple, lightweight, and unobtrusive, so as to be relatively inconspicuous to the patient. Background Art

[0002] In the 1990s, advances in microfabrication technology enabled the mass production of medical microneedle devices.

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

[0004] Solid microneedles coated with a therapeutic substance have been used to deliver pharmaceutically active substances directly to the epidermis and dermis, thereby overcoming the strong barrier of the upper layer of the skin. Another treatment option uses dissolvable polymer microneedles encapsulating an active substance, which slowly release the active substance into the skin over time. Hollow microneedles can be used to deliver a liquid pharmaceutical composition into the skin via the needle lumen.

[0005] Sampling of tissue fluid for subsequent analysis can also be achieved by withdrawing fluid from the body through the needle lumen.

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

[0007] Microneedles can be provided in the form of a device configured to be manually actuated by a patient in a non-clinical environment (such as at home). The microneedles must be brought into contact with the skin surface and then pushed through the surface so that the microneedles extend into the underlying layer of the skin. The problem in the art is that users may lack confidence in using the microneedle device and thus be reluctant to fully embed the microneedles into the skin. As a result, the user may not be able to fully push the microneedles into the skin and thus may not be able to access deeper tissues. In addition, partially embedded microneedles may be more prone to displacement. After displacement, the microneedles may cause damage to the skin when dragged across the surface.

[0008] To assist applications, systems can be used that include a main device configured to contact the skin and a separate applicator device that is removed after the main device has been applied to the skin. These systems are difficult to use and expensive to manufacture.

[0009] Another problem that arises is that the patient may not be certain whether the microneedles are correctly embedded in the skin in the first place. For the patient, it can be difficult, if not impossible, to observe the skin surface to check whether the microneedles are correctly embedded. If in doubt, the device can be removed and a new one applied to the skin. When the microneedles have actually been correctly embedded, replacing the device would be a waste.

[0010] Another problem with microneedle devices is that they are generally conspicuous and thus easily noticed by patients and others. The device may catch on clothing or any other nearby object, causing complete or partial displacement. These devices may need to be worn overnight, which can cause significant discomfort when the patient rolls onto the device.

[0011] Another problem is that prior art microneedle devices are complex and have a large number of separate components. This increases the cost and also increases the likelihood of failure. The large number of components also increases the weight of the device, thereby increasing the interference to the patient. It has been found that the discomfort associated with the weight increases proportionally with the duration of wearing the device. For some applications (such as hormone monitoring), continuous real-time data may be required for several weeks. Although the device may be replaced several times during this period, the problem of the patient wearing a heavy object for a long time still exists.

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

[0013] The discussion of documents, acts, materials, devices, articles, etc. incorporated in this specification is for the purpose of providing the context of the present invention only and does not imply or represent that any or all of these form part of the prior art base or are common general knowledge in the field related to the present invention, as they existed before the priority date of each claim of this application. Summary of the Invention

[0014] In a first aspect, but not necessarily the broadest aspect, the present invention provides a device for bringing one or more protrusions into contact with a patient's skin for a long time, the device comprising:

[0015] One or more protrusions, each configured to penetrate the skin;

[0016] A skin contact portion defining a skin contact surface and one or more spaces allowing the one or more protrusions to extend therethrough; and

[0017] A movable portion configured to move the one or more protrusions from a first position behind the skin contact surface to a second position protruding beyond the skin contact surface;

[0018] Wherein the device is configured to maintain the one or more protrusions in a first state where they cannot contact the patient's skin until the user actuates the device, the actuation causing or allowing the one or more protrusions to transition to a second state where they are fully embedded in the skin, and the device is further configured to (i) inhibit or prevent the one or more protrusions from transitioning back to the first state after actuation, or (ii) require an intentional action by the user or another user to transition the one or more protrusions back to the first state after actuation.

[0019] In an embodiment of the first aspect, the device includes a holding portion configured to hold the skin contact surface in contact with the skin during use.

[0020] In an 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.

[0021] In an embodiment of the first aspect, the non-linear path is a generally arcuate path.

[0022] In an embodiment of the first aspect, the movable portion has a connecting end and a free end.

[0023] In an embodiment of the first aspect, the free end travels a greater distance than the connecting end.

[0024] In an embodiment of the first aspect, the non-linear path is described with reference to the free end.

[0025] In an 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.

[0026] In an embodiment of the first aspect, the angular measurement 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°.

[0027] In an embodiment of the first aspect, the movable portion has a pivot portion, a hinge portion, a flexure portion, or an attachment portion.

[0028] In an embodiment of the first aspect, the movable part is associated with the mounting part.

[0029] In an embodiment of the first aspect, in use, the mounting part is fixed and the movable part is movable relative to the mounting part.

[0030] In an embodiment of the first aspect, the mounting part includes a portion that allows the movable part to pivot, articulate, bend, or attach.

[0031] In an embodiment of the first aspect, the mounting part presents a fixed spacing relationship with the skin contact surface.

[0032] In an embodiment of the first aspect, the mounting part is spaced from the skin contact surface by less than about 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, or 2 mm.

[0033] In an embodiment of the first aspect, the mounting part is generally located on the side of the movable part.

[0034] In an embodiment of the first aspect, the device further includes a user-actuatable release part, and the user can actuate the release part which is configured to hold the movable part in the first position until the user actuates the release part when the movable part is released and allowed to move to the second position.

[0035] In an embodiment of the first aspect, the device further includes a locking part which is configured to lock the movable part when in the second position.

[0036] In an embodiment of the first aspect, the device is constructed such that the movement of the movable part from the first position to the second position requires power from within and / or outside the device.

[0037] In an embodiment of the first aspect, the power within the device is derived from a spring, an elastically deformable member, a shape memory member, or other biasing means. The power outside the device comes from the user.

[0038] In an embodiment of the first aspect, the device is not configured with an internal power generator for moving the movable part from the first position to the second position.

[0039] In an embodiment of the first aspect, the holding part is a dermatologically acceptable composition disposed on or around the skin contact surface, or includes a dermatologically acceptable composition disposed on or around the skin contact surface.

[0040] In an embodiment of the first aspect, the dermatologically acceptable composition is an adhesive or its functional equivalent.

[0041] In one embodiment of the first aspect, the holding portion is configured to mechanically hold the skin contact surface in contact with the skin.

[0042] In one embodiment of the first aspect, the holding portion is selected from any one or more of the following: a strap, a band, a belt, a clip, a grip, a tie, a button, a sleeve, a stocking, a sock, a glove, a cap, a hat, underwear, a vest, a shirt, a bra, a top, pants, a scarf, a ring, glasses, and a collar.

[0043] In one embodiment of the first aspect, one or more protruding portions are directly or indirectly mechanically connected to the moving portion.

[0044] In one embodiment of the first aspect, one or more protruding portions are wires, needles, and / or microneedles.

[0045] In one embodiment of the first aspect, one or more protruding portions form an array.

[0046] In one embodiment of the first aspect, one or more protruding portions have a sufficient length to be able to contact the epidermis, dermis, or subcutaneous tissue of a patient.

[0047] In one embodiment of the first aspect, one or more protruding portions are configured to function in use so as to: conduct an electric current to, from, or through the skin; conduct a sound wave to, from, or through the skin; conduct light to, from, or through the skin; conduct heat to, from, or through the skin; sample a liquid or tissue from the skin; deliver a bioactive substance to the skin; or introduce an analytical sensing substance into the skin.

[0048] In one embodiment of the first aspect, one or more protruding portions are all conductive, and the device further includes a circuit having an audio, visual, or tactile indicator, the circuit being configured to actuate the indicator when one or more protruding portions come into contact with a conductive liquid naturally present in the skin.

[0049] In one embodiment of the first aspect, the circuit includes at least two protruding portions, and the circuit is configured to be completed through at least two protruding portions that contact a conductive fluid naturally present in the skin, thereby actuating the indicator.

[0050] In one embodiment of the first aspect, the circuit includes a protruding portion and at least one conductive pad placed against the skin, and the circuit is configured to be completed by electrical communication between the protruding portion and the pad with a conductive fluid naturally present in the skin so as to actuate the indicator.

[0051] In an embodiment of the first aspect, the device includes a housing sized such that when the device is applied to the skin and the movable part is in the second position, and any part of one or more protruding portions protruding from the skin contact surface is embedded in the skin, most or substantially all of the housing extends no more than about 5 millimeters, 6 millimeters, 7 millimeters, 8 millimeters, 9 millimeters, 10 millimeters, 11 millimeters, 12 millimeters, 13 millimeters, 14 millimeters, 15 millimeters, 16 millimeters, 17 millimeters, 18 millimeters, 19 millimeters, or 20 millimeters above the skin.

[0052] In an embodiment of the first aspect, the extended 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.

[0053] In an embodiment of the first aspect, the device is configured such that one or more protruding portions are inseparable from the device or are not separable from the device without the aid of a tool.

[0054] In an embodiment of the first aspect, the movable part and the mounting part are integral.

[0055] In an embodiment of the first aspect, the integral movable part and mounting part are made of an elastically deformable material.

[0056] In an embodiment of the first aspect, the integral movable part and mounting part are part of the circuit board of the device.

[0057] In an embodiment of the first aspect, the movable part is biased towards the second position and held in the first position, and resists the bias of the user-actuable release part until the release part is actuated, at which point the movable part is released and allowed to move to the second position.

[0058] In an embodiment of the first aspect, the user-actuable release part is a flange configured to hold the movable part in the first position, and the force provided by deforming the flange and / or the movable part by the user allows the movable part to be released from the flange and move to the second position.

[0059] In an embodiment of the first aspect, the movable part is hingedly connected to the skin contact part.

[0060] In an embodiment of the first aspect, the hinge is provided at or towards the peripheral region of the movable part and the skin contact part.

[0061] In an embodiment of the first aspect, the release portion includes a member configured to hold the movable portion in a first position but removable or deformable by a user to allow the movable portion to move to a second position.

[0062] In an embodiment of the first aspect, the member can be removed by sliding substantially across the skin contact portion.

[0063] In an embodiment of the first aspect, the member is substantially wedge-shaped, and the device includes a hinge that associates the movable portion with the skin contact portion, and a thin portion of the wedge-shaped member disposed near the hinge and a thick portion of the wedge-shaped member disposed away from the hinge.

[0064] In an embodiment of the first aspect, the release portion is removable from the device and includes a gripping portion to facilitate manual removal.

[0065] In an embodiment of the first aspect, the device is configured such that the transition of one or more protruding portions from a first state to a second state can be achieved by a single actuating action performed by a user portion on a device component, or by the user moving the device component in a single direction.

[0066] In an embodiment of the first aspect, the single actuating action or movement in a single direction is selected from: pushing, pulling, pressing down, compressing, rotating, twisting, bending, squeezing, stretching, separating, breaking, joining, turning, reorienting, hitting, tapping, and shaking.

[0067] In an embodiment of the first aspect, the device is configured such that once the transition begins, (i) the user cannot reverse it, or (ii) an intentional action of the user or another user is required.

[0068] In an embodiment of the first aspect, the device is configured such that the transition is completed in less than about 1 second, 900 milliseconds, 800 milliseconds, 700 milliseconds, 600 milliseconds, 500 milliseconds, 400 milliseconds, 300 milliseconds, 200 milliseconds, 100 milliseconds, 90 milliseconds, 80 milliseconds, 70 milliseconds, 60 milliseconds, 50 milliseconds, 40 milliseconds, 30 milliseconds, 20 milliseconds, 10 milliseconds, 9 milliseconds, 8 milliseconds, 7 milliseconds, 6 milliseconds, 5 milliseconds, 4 milliseconds, 3 milliseconds, 2 milliseconds, or 1 millisecond.

[0069] In an embodiment of the first aspect, the device is configured such that the transition is substantially real-time.

[0070] In an embodiment of the first aspect, the device is configured such that the start or completion of the transition is associated with a tactile, auditory, or visual feedback signal to the user.

[0071] In an embodiment of the first aspect, one or more protruding portions extend from a body that is acted upon during the transition.

[0072] In one embodiment of the first aspect, the transition involves the movement of one or more protrusions from a first position to a second position.

[0073] In one embodiment of the first aspect, the device includes a latching mechanism configured to prevent one or more protrusions from moving from the first position until a user applies a force of at least a threshold level to a component of the device through an actuation action, and once the force of at least the threshold level is applied, causes or allows the one or more protrusions to transition to the second position in a time less than about 100 milliseconds, 90 milliseconds, 80 milliseconds, 70 milliseconds, 60 milliseconds, 50 milliseconds, 40 milliseconds, 30 milliseconds, 20 milliseconds, 10 milliseconds, 9 milliseconds, 8 milliseconds, 7 milliseconds, 6 milliseconds, 5 milliseconds, 4 milliseconds, 3 milliseconds, 2 milliseconds, 1 millisecond or substantially in real time.

[0074] In one embodiment of the first aspect, the latching mechanism includes an elastically deformable structure that must deform to allow the one or more protrusions to move from the first position to the second position.

[0075] In one embodiment of the first aspect, the elastically deformable structure is associated with the one or more protrusions or with another component of the device.

[0076] In one embodiment of the first aspect, the other component is a component that remains stationary during actuation.

[0077] In one embodiment of the first aspect, the other component is the housing of the device, or a component of the device that contacts the skin of the patient of the application device, or a component of the device through which the one or more protrusions extend.

[0078] In one embodiment of the first aspect, the latching mechanism locks the one or more protrusions in the second position after device actuation.

[0079] In one embodiment of the first aspect, the device includes a body with one or more protrusions extending therefrom, wherein the latching mechanism includes a portion extending from the body.

[0080] In one embodiment of the first aspect, the device includes a biasing tool configured to maintain the one or more protrusions in the first position until actuation occurs, or to rapidly move the one or more protrusions from the first position to the second position, or to maintain the one or more protrusions in the second position after actuation has occurred.

[0081] In an embodiment of the first aspect, the device includes one or more fasteners configured such that when one or more protrusions move from a first position to a second position, the one or more fasteners are configured to allow the one or more protrusions to move towards the second position but prevent the one or more protrusions from moving back towards the first position.

[0082] In a second aspect, the present invention provides a method for bringing a protrusion into contact with a patient's skin, the method comprising the steps of: providing a device according to any embodiment of the first aspect, bringing the skin contact surface of the device into contact with the patient, and causing or allowing the movable part to move from a first position to a second position along a non-linear path.

[0083] In an embodiment of the second aspect, the device remains in contact with the skin for more than about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours or 96 hours. BRIEF DESCRIPTION OF THE DRAWINGS

[0084] FIG. 1 schematically illustrates in a side view a microneedle insertion device of the present invention. This embodiment relies on a biasing tool to provide the power for inserting the microneedles into the skin. When presented to the user, the arm is shown in a first position (20a), and when the microneedles are inserted into the skin, the arm is shown in a second position (20b). The curvature of the movable arm is deliberately exaggerated to better illustrate the operation of the entire embodiment. Although such a curvature is operable (and thus not excluded from the scope of the present invention), this curvature generally has a substantially lower magnitude;

[0085] FIG. 2A schematically illustrates in a side view another microneedle insertion device of the present invention. This embodiment relies on the user to provide the power for inserting the microneedles into the skin. When presented to the user, the arm is shown in a first position (205a), and when the microneedles are inserted into the skin, the arm is shown in a second position (205b);

[0086] FIG. 2B illustrates a variant of the embodiment of FIG. 2A without an upper housing;

[0087] FIG. 2C illustrates a variant of the embodiment of FIG. 2A having a toothed element (56) engaging a structure (57) on the arm to provide a ratchet-like mechanism to ensure unidirectional travel of the arm;

[0088] Figure 3A shows an upper perspective view of an embodiment of the present invention, which utilizes a printed circuit board (PCB) as a biasing tool to provide the power for inserting the microneedles into the skin. When presented to the user, the arm (20) is shown in a first position presented to the user and before the microneedles are embedded in the skin;

[0089] Figure 3B shows the embodiment of Figure 3A, but as a lower perspective view;

[0090] Figure 4 shows an upper perspective view of the microneedle embedding device of the present invention. This embodiment relies on the user to provide the power for inserting the microneedles into the skin. When presented to the user, the arm is shown in a first position and before the microneedles are embedded in the skin;

[0091] Figure 5A shows a lower perspective view of the embodiment of Figure 4;

[0092] Figure 5B shows an upper perspective view of the embodiment of Figure 4;

[0093] Figure 6 shows a lower perspective view of the embodiment of Figure 4, more completely showing the removable flexible layer, and the removable flexible layer is removed to expose the dermatologically acceptable adhesive;

[0094] Figure 7 shows a lower perspective view of the microneedle embedding device of Figure 6, and the removable flexible layer is removed to expose the dermatologically acceptable adhesive;

[0095] Figure 8A shows a lower perspective view of the microneedle embedding device of Figure 7, and the microneedles are in an extended position according to the need to embed in the patient's skin;

[0096] Figure 8B shows another microneedle device of the present invention, and the another microneedle device includes a temperature sensor. The device is further configured to prevent the microneedles from extending outward until the device is applied to the skin surface. The central area of the drawing shows the components of the device in a side view and exploded form. Each component is shown in a perspective view in the peripheral area of the drawing;

[0097] Figure 9 highly schematically shows a side view of the microneedle embedding device of the present invention, having a suction cup-like mechanism, and the suction cup-like mechanism inhibits the upward movement of the microneedles during actuation and further maintains the device on the skin after the microneedles are fully embedded. Figure 9A is before actuation, and Figure 9B is after actuation;

[0098] Figure 10 highly schematically shows a side view of the microneedle embedding device of the present invention, having opposing inclined surfaces, and the opposing inclined surfaces cooperate during actuation to embed the microneedles into the skin. Figure 10A is before actuation; Figure 10B is after actuation;

[0099] Figure 11 schematically shows, in a side view, the microneedle insertion device of the present invention, having a rotatable knob with an inclined surface that mates with a complementary inclined surface connected to the microneedle. The user rotates the knob to actuate the device and push the microneedle downward into the skin. Figure 11A is before actuation; Figure 11B is after actuation; Figure 11C shows the inclined surface in a perspective view;

[0100] Figure 12 schematically shows, in a side view, the microneedle insertion device of the present invention having a movable shutter and a leaf spring arrangement. Actuation of the device is achieved by the user sliding the shutter, which in turn allows the leaf spring to unfold and push the microneedle downward into the skin. Figure 12A is before actuation; Figure 12B is after actuation;

[0101] Figure 13 schematically shows, in a side view, the microneedle insertion device of the present invention having a helical spring-loaded arm held in a compressed state by a notched plate. Actuation of the device is achieved by the user sliding the plate, which in turn allows the spring to unfold and push the microneedle downward into the skin. Figure 13A is before actuation; Figure 13B is after actuation;

[0102] Figure 14 schematically shows, in a side view, the microneedle insertion device of the present invention having a bladder. Actuation of the device is achieved by the user squeezing a sphere to inflate the bladder, which in turn pushes the microneedle downward into the skin. Figure 14A is before actuation; Figure 14B is after actuation;

[0103] Figure 15 schematically shows, in a side view, the microneedle insertion device of the present invention, which includes a flange in a housing, and the flange serves to allow the microneedle to be in a retracted or extended state. Actuation of the device is achieved by the user pushing a button to force the button past the flange, and then the flange is used to lock the microneedle in the extended state (i.e., inserted into the skin). Figure 15A is before actuation; Figure 15B is after actuation;

[0104] Figure 16 schematically shows, in a side view, the microneedle insertion device of the present invention having a button with a tapered shaft. Actuation of the device is achieved by the user pressing the button to force the tapered shaft through a collar in the housing, where the wide end of the taper is locked behind the lip of the collar. In the locked position, the microneedle remains inserted into the skin. Figure 16A is before actuation; Figure 16B is after actuation;

[0105] Figure 17 schematically shows, in a highly schematic side view, a microneedle insertion device of the present invention having a frangible arm supporting microneedles. Actuation is achieved by pressing the device against the skin to break the arm, which in turn releases the microneedles and allows the springs to push them into the skin. Figure 17A is before actuation; Figure 17B is after actuation; and

[0106] Figure 18 schematically shows, in a highly schematic side view, a microneedle insertion device of the present invention having a buckling skirt that transitions from a first state in which the microneedles are retracted under the action of a force applied by a user to a second state in which the microneedles are inserted into the skin. Figure 18A is before actuation; Figure 18B is after actuation. Detailed Description

[0107] Unless otherwise specified herein, when used across different figures, features of figures labeled with the same number are considered to be the same features, or at least functionally similar features.

[0108] The figures are not prepared in accordance with any specific scale or dimension and are not presented as a completely accurate representation of the various embodiments.

[0109] After considering this embodiment, those of ordinary skill in the art will be clear on how to implement the present invention in various alternative embodiments and alternative applications. However, although various embodiments of the present invention will be described herein, it should be understood that these embodiments are presented by way of example only and not by way of limitation. Therefore, the description of various alternative embodiments should not be construed as limiting the scope or breadth of the present invention. In addition, statements of advantages or other aspects apply to specific exemplary embodiments and not necessarily to all embodiments, or indeed any embodiment covered by the patent application scope.

[0110] Throughout the embodiments of this specification and the patent application scope, the word "comprising" and variations of this word, such as "including", are not intended to exclude other additives, components, wholes, or steps.

[0111] References throughout this specification to "an embodiment" or "one embodiment" mean that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment of the present invention. Thus, the phrases "in an embodiment" or "in one embodiment" that appear in various places throughout this specification do not necessarily all refer to the same embodiment, but may refer to the same embodiment.

[0112] As used herein, when the device of the present invention is applied to the upward region of a patient's skin (e.g., the upper surface of a human thigh when a person is sitting on a chair), positional terms such as "lateral", "across", "above", "over", "below", "higher", "lower", "upward", "downward", "plan view" and similar terms shall be with reference to the device of the present invention. It should be understood that the device can be applied to a skin region having an orientation different from the upright orientation just defined, in which case those of ordinary skill in the art can adequately rephrase the foregoing positional terms.

[0113] The term "patient" is used to refer to an animal (including human and non-human animals) to which the present device can be applied. The term "user" is used to refer to a person who applies the device to a human or non-human animal. The patient and the user can be the same human subject, but not necessarily so.

[0114] Unless the contrary intention is apparent from the context of use, the terms "needle", "microneedle" and "thread" can be used interchangeably. Each is functionally the same or similar and capable of being inserted into a patient's skin to contact a biological fluid.

[0115] "Biological fluid" can be any biological fluid of a patient, including but not limited to interstitial fluid (ISF), blood, saliva, lacrimal secretions, lactation secretions, nasal secretions, 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, hepatic secretions, bile or exudates, any one of which contacts the needle electrode of an in vivo electrochemical sensor during use. "Tissue" includes a volume containing one or more cells.

[0116] The present invention discloses various different embodiments (whether through the accompanying drawings or written description), which have one or more features disclosed in their context. It should be understood that there is no intention to limit the application of specific features or combinations of features used in the disclosed embodiments. For example, the first embodiment is disclosed as including features A and B, while the second embodiment is disclosed as including features C and D. It is intended that embodiments including any one, two, three or four of the features A, B, C and D in any feasible combination be included within the scope of the present invention.

[0117] However, it will be obvious to those of ordinary skill in the art that certain combinations are less preferred or actually taboo. For example, when feature B requires feature A to operate, an embodiment including the combination of features B, C and D may not be feasible.

[0118] The present invention is at least in part based on the discovery that improved or alternative devices for inserting a needle into a patient's skin include a movable part that pushes a microneedle into the patient's skin in a controlled manner. Control aspects will be described more fully below.

[0119] The movable part may travel along a non-linear path. Additionally, the non-linear path may have a finite length and the path is a finite number of arcs. Through this arrangement, the main moving part of the device only requires a limited range of motion in the vertical direction to press the microneedle against the patient's skin and insert it into the patient's skin. When viewed from the lateral direction, the limited range of motion allows the housing of the device to present a relatively low profile. Thus, the device rises to a relatively small height above the skin and is therefore less obtrusive to the patient.

[0120] Furthermore, the non-linear path of the movable part allows for the use of simplified mechanisms. For example, the movable part may be moved through a simple bending or hinging mechanism. These mechanisms require a relatively small number of parts, thus allowing for the overall development of a smaller, lighter, simpler, more reliable, and less expensive device.

[0121] Certain embodiments of the present invention have further features that, either alone or in combination with other features, provide further advantages over the prior art or further useful alternatives. Such embodiments will be described more fully with reference to the non-limiting preferred embodiments described below.

[0122] Please refer to FIG. 1. FIG. 1 illustrates the basic form of the device (10), which has a microneedle array (one microneedle is labeled 15) attached to a movable part, which in the embodiment is an elastically deformable arm (20). The arm (20) is biased to present a linear configuration (20b), however, initially presented to the user is the arm bent into an upward curve, as shown by the dashed line (20a).

[0123] The device (10) includes a rigid housing (25) that has a skin contact portion (30) on its lower side, and the skin contact portion (30) defines a downward-facing skin contact surface (35). The surface (35) is placed on the patient's skin and is retained therein by areas of a dermatologically acceptable adhesive (40a, 40b). Suitable adhesives are generally capable of being waterproof to allow the patient to bathe normally. The adhesive generally has sufficient adhesion to inhibit detachment that may occur during daily activities such as dressing, undressing, sleeping, doing housework, light to moderate-intensity physical activities, rubbing against objects while walking, and similar daily activities. The degree of the adhesive is generally not so high as to cause any difficulty, unpleasant sensation, pain, irritation, or skin damage upon removal of the device.

[0124] Exemplary adhesives are synthetic rubber adhesives or tackified acrylic adhesives for use in medical tape types. A double-sided medical tape can be used, such as 3M TM Tape 1577, with one side adhered to the device and the other side adhered to the patient's skin.

[0125] The skin contact portion (30) includes a space (45) whose edges are marked (45a) and (45b). The space (45) provides a corresponding passage for the microneedles (15) to pass through, allowing the end regions of the microneedles to pierce and embed into the underlying skin (50) when the arm (20) is in the linear position (20b).

[0126] The arm (20) is held in its bent state by a flange (55) acting as a release device. When the user wishes to insert the microneedles (15) into the skin (50), they press the button (60) as indicated by the arrow. The lower surface of the button (60) rests on the flange (55), and since the flange (55) has a certain deformability (e.g., made of a rubber-like material or formed by a flexible protrusion on the inner surface of the housing (25)), it bends downward under the force, thereby releasing the edge of the arm (20a). The elastic nature of the arm (20a) causes it to quickly return to its biased linear position (20b), thus forcing the microneedles (15) into the underlying skin (50). The flange (55) is configured to exhibit sufficient elasticity to resist the biasing force in the arm (20a), yet this elasticity is insufficient to resist the downward force applied by the button (60) when pressed.

[0127] In the embodiment of Figure 1, one end of the arm (20) is fixed to the housing (25) through a fastener (63). Although the arm (20) is flexible, the flexibility is not so high that it easily moves away from the position (20b) when in place on the skin (50) of an object. As will be understood, any movement of the arm (20) away from the position (20b) may cause the microneedles (15) to retract from the skin (50). Given the biasing of the arm (20) towards the position (20b), a locking mechanism may not be required to hold the arm in the position (20b). However, if needed, a suitable locking mechanism will be described below for the embodiment of Figure 2A.

[0128] Figure 2A shows an alternative basic form of the device (200), where the arm (205) is rigid and hinged to the housing (25) via a hinge pin (210). In terms of the flange (55) acting as a release device, the operation of the embodiment of Figure 2A is similar to that of Figure 1. 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 flange (55), causing the flange (55) to bend and thus release the free end of the arm (205a). The button (215) continues to be pressed by the user until the arm occupies the position (205b), and in this position the microneedles (15) penetrate the skin (50). Similarly, the point on the free end of the arm (205a) travels along a non-linear path, and in this embodiment, the path is an arc that is part of a circle, with the origin of the circle located at the hinge pin (210).

[0129] It should be understood that the hinge device of the embodiment of Figure 2A does not provide resistance to the arm (205) hinging away from the position (205b) when wearing the device. Therefore, there is a risk of the microneedles (15) withdrawing from the skin (50) when in place. Therefore, a locking mechanism is provided to hold the arm in the appropriate position (205b). This mechanism includes a deformable latch (220), which is made of, for example, a material with a certain flexibility or an internal protrusion formed from the material of the housing (25). The latch (220) has an inclined upper surface, and when in contact with the rigid arm (205), the entire latch (220) is forced to bend to the left (as shown) under the force applied by the user through the button (215) and the action of the inclined upper surface. Once the end of the arm (205) crosses the lower corner of the inclined upper surface, the latch (220) returns to its normal upright position (as shown), and the free end of the arm (205b) is firmly fixed in the recess of the inclined upper surface at the base of the latch (220).

[0130] An alternative to the embodiment of Figure 2A is shown in Figure 2B. In Figure 2B, the device (200) does not have an upper housing. The arm (205a) is held in place by the flange (55), and in this embodiment, the flange (55) can be removed by the user when applying the device (200) to the patient. After removing the flange (55), the arm (205a) is pressed down by the user to assume the second position (205b).

[0131] In the embodiments of FIGS. 1, 2A and 2B, it will be noted that when released from the flange (55), the free end of the arm (20 or 205) moves in a non-linear manner when returning to the biased position (20b). If one considers a single point on the free end of the arm (20 or 205), that point travels along a non-linear path that depicts an arc. In the context of the present invention, the terms "arc", "arcuate" and similar terms refer to a curve connecting any two points. The term "arc" should not be restrictively interpreted as only representing a segment of a circle, although in some embodiments it is a segment of a circle (see, for example, the embodiment of FIG. 2A).

[0132] It can be clearly seen from the basic embodiments of FIGS. 1, 2A and 2B that in each case, when transitioning from the first position to the second position, the arm (20 or 205) travels a relatively small distance. In fact, in these embodiments (and certain other embodiments), the device is intentionally configured such that the arm cannot travel along any path other than the path between the first and second positions. In other words, the device can be configured such that the arm cannot travel along any path other than the shortest distance between the first and second positions.

[0133] By restricting the path along which the arm can travel, there is the advantage that the height of the device (in the vertical direction, as shown) is also restricted. Thus, this device can extend a relatively short distance above the patient's skin and present a low profile (in the sense of size).

[0134] Now turning to FIGS. 3A and 3A, there is shown a preferred device construction of an embodiment that generally follows FIG. 1 and operates generally in accordance with the embodiment of FIG. 1. The arm (20) is integrally formed with a PCB (65) that carries various electronic components required for the operation of the device. The PCB material is elastically deformable, allowing the arm (with micro needles attached at the terminals) to bend upward when the arm is positioned in the first position, but when released, assumes the second position due to the natural bias of the arm towards the second position.

[0135] The arm (20) is held in the first position by the end of the arm (20) resting on the flange (55), as most clearly depicted in FIG. 1A. In this position, the micro needles (15) are retained within the device and no part extends through the space (45). In this configuration, the device is provided for use and wherein the device is applied to the skin of a patient.

[0136] The arm (20) is connected to a microneedle mounting block (70) that supports the microneedles. The mounting block (70) also includes a conduit (not shown) to conduct electrical current from each microneedle (15) to one of a plurality of connection points (75) on the PCB (65). Through this arrangement, electrical signals can be transmitted to and / or from the microneedles embedded in the patient's skin. For example, the device can be configured as a sensor with microneedles that are configured to contact a biological fluid within the patient's body to detect an analyte therein. The biological fluid can be, but is not limited to, interstitial fluid, blood, or a mixture thereof. The electrical signals from the microneedles are transmitted to the PCB for amplification, filtering, encoding, analysis, transmission, or any other electrical or electronic process.

[0137] In this embodiment, the PCB has a dual function of carrying the electronic device and also serving as a power means for moving the microneedles from an internal position of the device to an external position. It has been found that the PCB material is well suited to provide a preferred limited range of motion for the arm of the device. Through this arrangement, the number of components in the device is reduced.

[0138] The upper surface of the housing (25) exposes the actuation surface of a button (215) that can be depressed by a user's finger. The button (215) is biased upwardly (as shown) by a spring or due to the button (215) being integrally formed with the housing (25) material. In the latter biasing form, the button (215) can be mounted on an arm integral with the housing material and is biased such that the upper surface of the button (215) is coplanar with the housing (25).

[0139] The lower portion (not visible) of the button (215) presses against the upper surface of the arm (20), which is the rear surface of the PCB (65), such that depressing the button (215) will push the arm (20) downward to release from the flange (55) and assume a second position. In the second position, it should be understood that the microneedles will extend through the respective spaces (45) and embed in the underlying skin (e.g., the patient's epidermis, dermis, or subcutaneous tissue).

[0140] The natural bias of the PCB (65) material towards the second position is strong enough for the arm (20) to remain in the second position without any means of locking the arm in the second position. Thus, the microneedles (15) are able to remain embedded in the patient's skin for an extended period of time.

[0141] 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 bias of the arm (20) towards the second position is not strong enough to prevent any movement away from the second position. In such an embodiment (and other embodiments), a locking mechanism can be provided to prevent the arm from moving away from the second position, such that the microneedles (15) do not retract into the device and remain embedded in the skin. A suitable locking mechanism is the latch mechanism as disclosed in other embodiments herein. Other locking mechanisms will be apparent to those of ordinary skill in the art who benefit from this specification.

[0142] The housing (25) includes opposing recesses (80) to facilitate gripping between the user's thumb and middle finger and to hold the device on the skin surface. The user's first finger can freely actuate the button (215) to embed the microneedles (15) into the underlying skin.

[0143] The skin contact surface (35) can have a dermatologically acceptable adhesive layer (not shown) applied thereto to hold the device in place on the patient's skin for an extended period of time. The adhesive layer can cover a portion or substantially all of the skin contact surface (35). A manually releasable flexible layer can cover the adhesive until the device is applied to the skin, as described in other embodiments of the device herein.

[0144] Turning now to FIGS. 4, 5A, 5B, 6, and 7, there is shown a preferred device generally constructed in accordance with the embodiment of FIG. 2B and operating generally in accordance with the embodiment of FIG. 2B.

[0145] This embodiment includes an upper housing portion (25) and a skin contact portion (30). A removable flexible layer (90) that can be grasped through the protrusions (95) is also provided, the removal of which exposes the dermatologically acceptable adhesive on the skin contact surface (35). As described above, the purpose of the adhesive is to retain the device on the patient's skin for an extended period of time. The flexible layer (90) is used to prevent the adhesive from curing or drying, to prevent the adhesive layer from being contaminated prior to use, and / or to prevent the adhesive from prematurely adhering to the packaging or other surfaces. In a particularly preferred embodiment, in addition to covering the adhesive layer, the flexible layer (90) extends in the space (45) to prevent contamination of the microneedles (15) and also helps to prevent accidental needle stick injuries to the patient.

[0146] The device can have a holding portion that is used to hold the device on the skin such that the protruding portion remains in contact with the patient's biological fluid. The holding portion can be dedicated to this function or can perform another function.

[0147] In many cases, it will be useful for the retention portion to be or include a dermatologically acceptable adhesive. The adhesive allows the user to simply apply the device, typically only requiring removal of a protective backing sheet to expose the adhesive and then bringing the exposed adhesive into contact with the skin. This method of application is similar to that of a plaster and is thus a process already familiar to users.

[0148] As an alternative to using an adhesive, the retention portion can be some mechanical means for holding the device in the desired position on the skin. For example, the device can include a specialized strap that engages around a limb and is adjustable to hold the device firmly applied to the patient. As an alternative, the device can be incorporated into a wearable item such as a glove or shirt, or into a jewelry item such as a ring for holding the device in place. The device can be configured to engage with a discrete wearable item (e.g., via complementary hook-and-loop means), or the wearable item can be integrally formed with it.

[0149] In some embodiments, the device is simply maintained by a wearable item against the housing. For example, the retention portion can be a form-fitting elastic glove worn over the device.

[0150] In some embodiments, the retention portion is any surface or part of the device that contacts the patient's skin, where the characteristics of the patient are at least partially responsible for maintaining the device in the proper position on the patient. For example, the device can be configured to be held between two parts of the body that are normally in close juxtaposition, or held within an existing anatomical structure. The shape and / or size of this device can be designed to be held between the toes, between the buttocks, in the groin, in the buccal cavity, in the nostrils, in the ear canal, or in the navel.

[0151] In other embodiments, the shape and / or size of the device housing is designed to fit closely over, for example, a finger, a toe, or an ear. The device housing can be elastically deformable, for example, composed of a rubber material, and is configured to stretch over any anatomical part (e.g., a finger).

[0152] Each of the above embodiments is considered a retention portion within the context of the present invention.

[0153] The device also includes a release member (100) having a gripping portion (105) and a wedging portion (110), the function of which will be described more fully hereinafter.

[0154] Now turning to the exploded views of FIGS. 5A and Figure 5B The components of FIGS. 5A and Figure 5B similar to those in the previous figures will be immediately apparent.

[0155] In this embodiment, the power for moving the arm (205) to push the microneedles (15) into the underlying skin is provided by the user. In use, the user places a finger on the upper housing (25) and pushes downwards. Additionally, the arm (205) is movable via a hinging means.

[0156] The hinging means is provided via opposing lugs (115) extending from the skin contact portion (30), each lug including a hole. The arm (205) includes opposing laterally extending discs (122), each disc being seated in the hole of a lug (115). Clearly, the arm (205) is capable of hinging relative to the skin contact portion (30) to permit movement from a first position to a second position.

[0157] The arm (205) is presented to the user with the arm in the first position. The arm (205) is held in the first position by the wedging portion (110) of the release member (100). Before removing the release member (100), the wedging portion is inserted between the skin contact portion (30) and the arm (205), thereby holding the microneedles within the device.

[0158] When it is intended to apply this device to the skin of a patient, the user removes the flexible layer (90) by pulling on the tab (95) to expose the adhesive layer on the skin contact surface (35). The device is then applied to the skin and held in place for an extended period by the adhesive.

[0159] Once the device has been applied to the skin, the user grasps the gripping portion (105) and pulls laterally to the left (as shown) so as to completely remove the release member (100). The release member (100) no longer has any function and is discarded at this time. By removing the release member (100), the arm (205) is released from the first position and allowed to move (under the downward force applied by the user) to the second position, whereby the lower surface of the arm (205) contacts the upper surface of the skin contact portion (30). In the second position, the microneedles (15) extend through the space (45) and into the underlying skin.

[0160] As will be understood, the release member (100) can be configured to prevent the upper housing (25) of the device from closing onto the skin contact portion (30) when not intended by the user. The release member (100) is inserted or otherwise juxtaposed between the upper housing (25) and the skin contact portion (30) to prevent the upper housing (25) from closing towards the skin contact portion (30) sufficiently to allow the tips (i.e., the protruding portions) of the microneedles to protrude from the bottom of the holes in the skin contact portion (30). Preventing the closing also prevents the arm (205) from moving from the first position to the second position. Thus, when the release member (100) is in place, the tips of the microneedles are not inadvertently touched, causing microneedle contamination or injury. In using this device, as a step in the use process, the user removes the release member (100). In a preferred embodiment of the use of the device, the user first adheres the device to the skin of the patient, then removes the release member (100), and then presses the upper housing (25) to insert the microneedles into the skin.

[0161] Before being removed by the user, the release member (100) can be held in place by any of a variety of features. In one example, the release member (100) includes a protrusion that fits into a recess in the upper housing (25), the skin contact portion (30), or both the upper housing (25) and the skin contact portion (30) to help retain it in place until it is deliberately 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 frictional force between the release member (100) and the upper housing (25) or with the skin contact portion (30) helps to hold it in place until it is intentionally removed. In another example, magnetic force can be used to help hold the release member (100) in place. In one embodiment of the present invention, when the release member (100) is in place, a magnet mounted within the release member (100) is positioned close to a Hall effect sensor located in 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 take some action, such as powering on an electronic circuit ready for use, switching it from a sleep mode to an active mode. It should be understood that the above are examples of possible methods for helping to hold the release member (100) in place before intentional removal, which can be used alone or in combination, and other methods known in the art can also be used alone or in combination with the given examples.

[0162] In some embodiments of the present invention, the release member (100) can also be used as a covering assembly for covering the microneedles after the device has been removed from the patient. In a preferred example of this embodiment, the locking assembly is located on the upper housing (25) and extends downwardly towards the skin contact portion (30). The release member (100) includes a groove that allows the release member (100) to slide over the locking assembly when the release member (100) is withdrawn from the device, while keeping the face of the release member (100) continuously facing the upper surface of the skin contact portion (30). In use, the release member (100) according to this preferred embodiment is removed by the user before the user presses the upper housing (25) to insert the microneedles into the patient's skin and is retained by the user. After the device is removed from the patient 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 microneedles. In another example of this embodiment, the release member (100) is flexibly attached to the device such that the release member (100) can remain attached to the device after it has been withdrawn by the user, and then, after the device has been removed from the patient after use, the release member (100) is repositioned to cover the protruding microneedles. In another example of this embodiment, the release member (100) and the upper housing (25) are designed such that the release member (100) is capable of slidably or otherwise engaging with the upper housing (25) once it has been removed, wherein the release member (100) is stored when the device is in use and is removed after the device has been removed from the patient for use as a covering assembly.

[0163] In some embodiments, the device is configured to facilitate removal of the device from the patient by the user. As will be appreciated, 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 such that there is a gap between the patient's skin and the surface (35), wherein the user uses this gap as a leverage point to help pull the device away from the skin by breaking the adhesive. In another example, a lever mechanism that is not located on the skin contact surface is incorporated to allow a greater gap than the gap created by the absence of adhesive on a portion of the skin contact surface. In another example, a protrusion that extends beyond at least one edge of the skin contact portion (30) and is attached to the adhesive layer can be incorporated, wherein the user pulls on the protrusion with sufficient force to cause the adhesive layer to stretch and yield, further causing the adhesive to delaminate from the skin contact surface (35) and the skin.

[0164] In some embodiments of the present invention, the device is designed such that the release member (100) is locked in place before use of the device, unless pressure is applied to the upper housing (25). This embodiment aims to further improve the risk of premature withdrawal of the release member (100). 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 can be lockingly engaged when the upper housing (25) is not pressed. When the upper housing (25) is pressed down, the features on at least one of the upper housing (25) and the skin contact portion (30) deform, thereby disengaging the release member (100) and allowing it to be withdrawn.

[0165] In yet other embodiments, the release member (100) does not need to be removed from the device by the user. According to these embodiments, the release member (100) includes a flexible assembly having a high enough stiffness such that when subjected to closing forces that may be present on the device during manufacturing, storage, and in the user's hand before application to the patient, the release member (100) will not substantially deflect, but is flexible enough that when the user deliberately applies a closing force to the device when applying the device to the patient's skin, the device will deflect. In such a deflection, the release member (100) deflects, thereby allowing the upper housing (25) to close towards the skin contact portion (30). In these embodiments, the release member (100) can also be used as a locking assembly, or the release member (100) can be separated from the locking portion. In some of these embodiments, for example, the feature labeled (220) in FIGS. 5A, 5B, and 7 can form the release member (100).

[0166] The dimensions of each space (45) of the device are designed such that the microneedles can clearly extend therethrough, and at least the tapered portion of the microneedles will not strike the sides of the holes during insertion. In some embodiments, the holes can have a sufficient cross-section such that no part of the microneedles will contact the sides of the space during insertion. In other embodiments, the holes will have such a cross-section along at least a portion of their length such that a portion of the length of the microneedles will contact the sides of the holes during insertion. According to this embodiment, the role of the holes is to help support a portion of the length of the microneedles to help prevent the microneedles from bending during insertion.

[0167] In some embodiments of this device, the skin contact portion (30) includes additional spaces or depressions that are configured to receive protrusions on the release member to help hold the release member until it is removed by the user. Additionally or alternatively, the skin contact portion (30) includes protrusions that are designed to be received in recesses in the release member to help hold the release member in place until intentionally removed by the user.

[0168] The embodiments illustrated in FIGS. 4, 5A, 5B, 6 and 7 include a locking portion in the form of a latch (220) that permanently locks the arm (205) in a second position, preventing any pivotal movement of the arm (205). In the illustrated embodiment, the latch (220) is a simple integral member that is deflectable in response to movement of the arm (205) towards the closed position, but then returns to its original position when the arm (205) is in the second position (205b), thereby locking the arm (205) in place.

[0169] The locking portion may act on another component of the device rather than on the arm (205), and that component in turn locks the arm in place. For example, the locking portion may act on the upper housing (25), and the upper housing (25) in turn holds the arm (205) in the second position. In another alternative, the locking portion may act on the PCB (65), and the PCB (65) in turn holds the arm (205) in the second position.

[0170] In other embodiments, the locking portion includes a recess into which a protrusion on the upper housing (25) is inserted to lock the upper housing (25) in the closed position (i.e., the arm (205) is in the second position). In one embodiment, the locking portion includes a flexible assembly designed to allow the locking portion to move when struck by the upper housing (25), thereby allowing the housing (25) to close relative to the skin contact portion (30), and thereby, once the upper housing (25) is closed, allowing the locking portion to move to lock the upper housing (25) in the closed position. In one embodiment, the device includes a protrusion on the upper housing (25) designed to be inserted into a recess in the locking portion, the protrusion including a flexible assembly to allow the protrusion to move, thereby allowing the upper housing (25) to close relative to the skin contact portion (30), and then after the housing (25) is closed relative to the skin contact portion (30), the protrusion moves to insert into the recess of the locking portion, thereby locking the upper housing (25) in the closed position. The flexible assembly may include a shaft that is deformable enough to allow the upper housing (25) to close without the shaft collapsing, such that the flexible assembly will attempt to return to its original position after the upper housing (25) is closed. In a less preferred but still effective embodiment, the flexible assembly includes a helical spring.

[0171] The flexible assembly of the locking portion may be made of any suitable material having the necessary stiffness and yield point. Examples of suitable materials include amorphous plastics, crystalline plastics, sprung steel, unsprung steel, stainless steel, or other materials known in the art having appropriate mechanical properties.

[0172] In a preferred embodiment of the present invention, the locking portion is made of the same material as the skin contact portion (30) to facilitate the manufacture of a skin contact portion with an integral locking portion.

[0173] In a particularly preferred embodiment of the present invention, the force required to deflect or otherwise move the flexible component is designed to be large enough such that the pressure that the user needs to provide to deform the flexible component and thus cause the upper housing (25) to close towards the skin contact portion is sufficient to insert the microneedles into the skin. According to this embodiment, the flexible component of the locking portion is used to set the force required to close the device (thus causing the arm to assume the second position) and to ensure that the force is sufficient to insert the microneedles into their intended position embedded in the skin.

[0174] In other embodiments, the locking portion includes at least one adhesive region located on at least one of the lower surface of the upper housing (25) and the upper surface of the skin contact surface (35). When the device is closed, one or more adhesive regions adhere the upper housing (25) to the skin contact portion (30), thereby locking the device in the closed position.

[0175] In another embodiment of the present invention, the locking portion can assume three different stable states. In the first state, the locking portion is in a disengaged configuration before the upper housing (25) is pushed downward towards the skin contact portion (30) to close the device. In the second state, the locking portion is in a first engaged position. When the locking portion is in the first engaged position, it is used to lock the microneedles (15) in their embedded position in the skin (i.e., the arm (205) is in the second position). In the third state, the locking portion is in a second engaged position. In this state, the locking portion locks the device in the open position (i.e., the arm (205) is in the first position), while the microneedles are retracted into the device to improve the likelihood of needle stick injury due to the protruding microneedles after device use. In an example of this embodiment, the locking portion includes a user engagement portion that can be grasped or otherwise engaged by the user, such as by engaging a fingernail under a hanging flange, such 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 place, as in the other embodiments disclosed herein. When it is necessary to remove the device from the patient, the user engages the locking portion and deflects the locking portion in a first direction, thereby unlocking 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., the arm is in the first position) while the microneedles are in the retracted position. In a preferred embodiment of this example, in the first direction, the locking portion moves away from the body of the device, and in the second direction, towards the body of the device. When fully deflected in the second direction, the locking portion is designed to stably engage, for example, in a recess to prevent the device from closing inadvertently.

[0176] In some embodiments of the present invention, when the microneedles are inserted into the skin, the downward force on the microneedles is provided by the flexible component of the locking part, and the downward force is applied when the device is locked in the closed position (i.e., when the movable arm is in the second position). In some embodiments, the effective locking of the movable arm in the second position is provided by a dedicated spring or other suitable biasing means. In other embodiments, the spring or other biasing means is not dedicated to the locking function and can also act as the power for moving the arm from the first position to the second position, for example. For example, a torsion spring can apply a closing torque at the pivot point (if any). In another example, a flat, disc-shaped or helical spring is mounted to the rear of the microneedle such that when the device is closed, the spring is twisted or compressed so as to apply a downward force on the microneedle when the device is in the closed position.

[0177] Although not an essential feature of the present invention, for many applications in which the microneedles are used to conduct current to, from, or through the skin, a PCB (65) will be required. In this regard, the PCB can 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 TM module). The device will of course include a power source, typically a button battery.

[0178] The embodiment shown in FIG. 3A further includes a light-emitting diode (LED) (120) visible to the user. One function of the LED (120) can be to confirm to the user and / or patient that the microneedles are correctly embedded in the skin during application and remain so during long-term wear.

[0179] The LED is electrically connected to the PCB (65), which is in turn electrically connected to the microneedles (15). The correct embedding of the microneedles can be determined by referring to any one or more of the current, current resistance, or impedance between two microneedles.

[0180] Alternatively, the correct embedding of a single microneedle can be determined by referring to any one or more of the current, current resistance, or impedance between a single microneedle and some other electrical contact of the device with the skin. As an example, a conductive pad can be placed on the surface of the skin, where in some examples, the conductive pad is placed on the surface of the housing in contact with the skin. When the microneedles are inserted into the skin, this conductive pad cooperates with at least one microneedle to complete the circuit. The completion of this circuit is used to indicate the correct insertion of the microneedles.

[0181] The electronic device involved may be very simple. Any example of skin biofluid, such as interstitial fluid (naturally conductive), will serve to complete the circuit including the LED. Assume that the simple contact of the microneedles with the biofluid shows correct insertion. The LED emits light where the microneedles contact the biofluid (and vice versa), thus providing a visual indication of correct insertion.

[0182] A more complex electronic configuration may be required to ensure a higher level of providing correct microneedle insertion. For example, it can be considered whether the microneedles of a minimum length are inserted, thus providing a guarantee of inserting the microneedles to a certain minimum depth. The device may include electronic means for measuring parameters such as current, with a higher current indication or more complete microneedle insertion. Program instructions executed by an on-board processor or otherwise associated with the device can use parameters such as current (possibly in combination with other physiological or environmental parameters) as input to provide an indication of the degree of microneedle insertion.

[0183] Another function of the LED can be to provide other information, such as the battery charge level. For example, the LED can be connected to a microprocessor capable of monitoring the battery voltage, and when the voltage is below a predetermined threshold, the microprocessor causes the LED to flash red. The predetermined threshold can be a voltage slightly higher than the minimum operating voltage to allow the patient time to use a replacement battery (or a replacement device where the battery is not user-serviceable) before the device becomes inoperable.

[0184] In other embodiments, the LED can produce an output indication of the data online status. For example, the LED can alternately flash red and green lights to warn of a wireless data connection interruption with a remote device such as a smartphone. The smartphone may be responsible for processing the sensor output and warning the patient through an audible output when a threshold is breached (such as the glucose concentration). In such an embodiment, the LED and the device networking module can be connected to a microprocessor that monitors the connection status of the module and causes the LED to produce an output when the connection is established and / or lost. Although the application software on the smartphone can be configured to warn the user of the loss of data connection, the smartphone may power off (e.g., due to battery depletion), in which case the only way to warn the patient is through the device itself.

[0185] A buzzer or a micro speaker can provide an output function similar to that of the LED to provide an audible output understandable by the patient. For example, the output can be a tone, a series of tones, or a synthetic voice.

[0186] Now refer to an alternative embodiment of the device shown in FIG. 8B, which is a modified version of the embodiments shown in FIGS. 4A to 8A. The embodiment of FIG. 8B includes a temperature sensor (900) that, in operation, extends through a space (905) in the skin contact portion (30) to contact the surface of the patient's skin. The temperature sensor (900) can be, for example, a thermocouple or a thermistor operably connected to a microprocessor on the PCB (65). The temperature sensor can be in direct contact with the skin or can be separated from the skin by a thermally conductive material.

[0187] The temperature sensor can be disposed within a pouch or other structure sized to accommodate the temperature sensor. The pouch can be made of a thin sheet of plastic material, such as a thermally conductive plastic with a metal or other filler, to facilitate the transfer of thermal energy from the underlying skin to the temperature sensor. The temperature sensor can be surrounded by a thermally conductive paste to facilitate the transfer of thermal energy from the pouch wall to the temperature sensor.

[0188] The bottom of the pouch can extend outward from the device such that when the device is applied to the skin surface, the bottom of the pouch is gently pushed against the skin surface, thereby facilitating the transfer of thermal energy from the skin to the temperature sensor. It should be understood that pushing the bottom of the pouch too forcefully against the skin surface may force blood out of the skin microvasculature, thereby artificially cooling the skin surface.

[0189] Preferably, only the bottom of the pouch is made of a thermally conductive material, and the remainder is made of a low thermal conductivity material. With this arrangement, thermal energy from the skin will not be dissipated away from the temperature sensor.

[0190] An insulating material can form the top of the pouch to ensure that thermal energy remains around the temperature sensor and is not lost to the interior cavity of the housing.

[0191] The pouch can include a space extending through the bottom such that the temperature sensor can be in direct contact with the skin surface. Given that no thermal energy needs to pass through any intermediate material, it is expected that the temperature will be closer to the actual skin temperature.

[0192] In a further modification, the temperature sensor can be an infrared sensor module, and in this case, the material of at least the bottom of the pouch should not substantially interfere with its operation. It can be contemplated that a space can be formed in the bottom to allow the infrared sensor module to be directly exposed to the skin surface for accurate reading of the skin temperature.

[0193] The signal output from the temperature sensor (900) can be used for calculations by a microprocessor (or a remote microprocessor) to more accurately determine the concentration of the target analyte. For example, the microprocessor can access a series of stored calibration curves, each curve being performed at a given temperature. Based on the output of the temperature sensor (900), an appropriate calibration curve can be selected and thus a more accurate analyte concentration can be determined.

[0194] The embodiment of FIG. 8B includes a release member (100) having paired protrusions (a first protrusion labeled 910, the second protrusion in the pair of protrusions being obscured by the first protrusion). The protrusion (910) extends downwardly and passes through a space (915) in the skin contact portion (30). The function of the protrusion (910) is to prevent the release member (100) from moving laterally until the lower surface of the skin contact portion (30) bears against the skin. The action of bearing against the skin causes the protrusion (910) to vertically depart from the space (915), thereby allowing the release member (100) to be laterally pulled away by an object. This mechanism prevents the release member (30) from being inadvertently removed before the device is properly applied to the skin surface. Without such a mechanism, the microneedles (15) may prematurely extend through the space (45) and may be contaminated by contact with air or an object, or may be physically damaged, for example, by snagging on clothing.

[0195] The device can be configured in the construction of a microneedle device to control the microneedles such that when applied to the skin and actuated by the user, the microneedles are unidirectionally pushed into the skin and become fully embedded therein. It is not allowed for the microneedles to be only partially embedded (i.e., extend into the dermal tissue to any depth less than required), nor is it allowed for the microneedles to withdraw from the skin during the embedding process.

[0196] When the microneedle device is applied to the skin of a patient (this process typically involves exposing the adhesive surface of the device and contacting it with the skin), the user actuates the device (e.g., by pressing a button), and according to the present invention, the microneedles are unidirectionally pushed through the skin surface and thus fully embedded in the underlying tissue in one operation. The device can be configured such that the user cannot pause the embedding process when the microneedles are not fully embedded, nor can the user reverse the embedding process to withdraw or partially withdraw the microneedles from the skin.

[0197] In some embodiments, the microneedles are locked in a fully extended state after being fully embedded. Without disrupting the adhesive (or any other means of holding the device to the skin), the microneedles remain fully embedded and thus are in full contact with the dermal tissue as required.

[0198] The device can also be configured such that the insertion of the microneedles occurs rapidly and, in some embodiments, essentially instantaneously. In this way, the user can actuate the device through the microneedles that are rapidly pushed into the skin. For example, a snap mechanism can be incorporated into the device, which in some embodiments requires the user to apply a minimal amount of force to the components of the device. Once the minimal force is applied, there is a sudden transition from a first state (e.g., no microneedles inserted) to a second state (e.g., full microneedle insertion). Advantageously, some positive tactile, visual, or auditory feedback is provided to the user to confirm that the device has been fully actuated.

[0199] The present device can offer advantages over the prior art because the user is able to confidently and reliably insert the microneedles fully into the patient's skin in a reproducible manner. Thus, the microneedles extend to the full depth required to reach the dermal tissue, such that the tips contact the tissue fluid of the target volume. This fluid can come into contact with the sensing aptamer or the drug conjugated to the microneedles, or can be withdrawn through the lumen in the microneedles for subsequent analysis.

[0200] Referring now to FIGS. 9A - 18B, which illustrate embodiments of a device in which microneedles extend from a body (300) that travels linearly between a first position and a second position. However, it should be noted that the embodiments of FIGS. 1 - 8B (where the microneedles are mounted on a member that travels in a non - linear manner) can be adapted to incorporate one or more features of FIGS. 9A - 18B and vice versa.

[0201] Considering FIGS. 9A - 9B, the function of the device is similar to a suction cup. The flexible skirt (305) seals the surface between the body (300) and the patient's skin (50). The button (215) is pushed down by the user (FIG. 9A), thereby discharging the air compressed below the skirt (305) through the one - way valve (310). When the button is fully depressed, the microneedles of the body (300) are fully inserted into the skin (50). It should be understood that when the button (215) is depressed, there will be some resistance to the upward movement of the button (and the withdrawal of any microneedles from the skin) because the one - way valve (310) does not allow the air below the skirt (305) to enter. An attempt to move the body (300) upward results in the formation of a vacuum below the skirt, and the vacuum acts to pull the body downward. Thus, the body (300) and its associated microneedles travel essentially unidirectionally towards the skin. In this embodiment, through the seal formed between the skirt (305) and the skin (50) and the vacuum generated below the skirt (305), the device can remain on the skin for an extended duration. When the device must be removed, the user can lift the edge of the skirt (305) to break the seal formed with the skin (50) below it.

[0202] In the embodiment of FIGS. 10A - 10B, the first wedge (315) is laterally moved by the user (FIG. 10A) so as to slide over the second wedge (320), thereby moving the latter downward and embedding the microneedles extending from the body (300) into the skin (FIG. 10B). The opposing surfaces of the first wedge (315) and the second wedge (320) may be frictionally engaged to some extent to resist any reverse movement of the first wedge (315) towards its original position. In one embodiment, the opposing surfaces are toothed so as to form a ratchet - like arrangement, thereby substantially preventing any reverse movement of the first wedge (315) and preventing withdrawal therefrom when the microneedles are fully embedded.

[0203] In the embodiment of FIGS. 11A - 11C, complementary inclined structures (325a, 325b) are provided on an axially rotatable knob (330) and a lower body (335), respectively. When the user rotates the knob (330), the lower body is pushed downward, and in turn acts on the body (300) to push the microneedles into the underlying skin. To prevent any reverse rotation of the knob (330), the outer periphery of the knob (300) may have a configuration that engages with a recess in the opposing face of the housing (25). Thus, under the action of the rotational force provided by the user, the structure enters and exits the recess to allow the knob (330) to rotate in the desired direction. In the absence of any applied rotational force, the structure remains in the recess to prevent any reverse rotation. When the knob (300) is fully rotated and the microneedles are fully embedded, the knob (300) is locked in place by juxtaposing respective vertical faces (one labeled 340) on the inclined structures (325a, 325b).

[0204] To actuate the embodiment of FIGS. 12A - 12B, the user laterally moves the movable shutter (345). Initially (FIG. 12A), the movable shutter (345) contacts the leaf spring (350), holding both in a compressed state. Thus, the leaf spring (350) is isolated from the body (300). When the movable shutter (345) slides to the right (FIG. 12B), the leaf spring (350) is allowed to extend through the movable shutter space so as to instantaneously press on the body (300), thereby quickly pushing the body downward. The biasing of the leaf spring (350) ensures that the movement of the body (300) is unidirectional (i.e., downward). The function of the helical spring (355) is to hold the movable shutter (345) in the outward position shown in FIG. 12A until actuation is required.

[0205] In the embodiment of FIGS. 13A - 13B, the body (300) is mounted on a spring - loaded arm (360). Before actuation (FIG. 13A), the vertical helical spring of the spring - loaded arm (360) is compressed behind the rim (361) of the arm (360). The arm (360) is held in the retracted state shown in FIG. 13A by a horizontal plate (362) which has a notch (363) against which the rim (361) abuts. To actuate the device and deploy the microneedles, the user laterally moves the plate (362) to displace the notch (363), thereby releasing the arm (360) and allowing the helical spring (360) to expand, thus moving the arm (360) rapidly downward (FIG. 13B). The downward movement of the spring - loaded arm (360) rapidly pushes the body (300) downward so as to fully embed the microneedles into the skin (50). After actuation, the helical spring holds the arm in the extended position shown in FIG. 13B, thereby preventing any withdrawal of the microneedles from the skin. The function of the horizontal helical spring (368) is to hold the plate (362) in the outward position shown in FIG. 13A.

[0206] The embodiment of FIGS. 14A - 14B includes a bladder (370) in gas communication with a compressible ball (375). To actuate the device, the user squeezes the compressible ball (375), as in FIG. 14A, causing the expelled air to pass through a one - way valve (380) and inflate the bladder (370). The inflation of the bladder then pushes the body (300) and the microneedles downward and into the skin (50), as shown in FIG. 14B. The one - way valve (380) prevents the microneedles from traveling in the opposite direction during actuation and also prevents the microneedles from being withdrawn after actuation.

[0207] In the embodiment of FIGS. 15A - 15B, the body (300) is directly connected to the button (215). A helical spring (385) biases the button (215) upwardly in readiness for actuation. The housing (25) has an upper annular flange (390) and a lower annular flange (400), each flange having a toothed profile. The button (215) has an annular flange (410) which has the same toothed profile as the housing, although inverted. Before actuation (FIG. 15A), the upward horizontal plane of the flange (410) abuts against the downward horizontal plane of the flange (390) through the action of the spring (385). When the button (215) is pressed, the flange (410) moves downwardly and contacts the flange (400), while the flange (410) deforms (or even the wall of the button (215) below the flange (410) deforms), thereby allowing the button (215) to be fully located at the bottom of the housing (25), as shown in FIG. 15B. When fully in position, the body (300) is at its lowest point and the microneedles are fully embedded in the skin (50). The lower flange (400) prevents the button (215) from moving upwardly and thus also prevents the microneedles from withdrawing. The upward horizontal plane of the face of the flange (410) abuts against the downward horizontal flange (400), thereby preventing relative movement between the button (215) and the housing (25).

[0208] Turning now to FIGS. 16A - 16B, this embodiment includes a button (215) that extends through a plate (415) and is connected to the body (300) at its end. This button has an annular flange (420) and a lower conical region (425) on its shaft. The plate (415) has a vertical shaft collar (430) extending from its upper surface, and the collar (430) has an inwardly turned lip (435). A helical spring (440) surrounds the collar (430) and the conical region (425) and biases the flange (420) and the plate (415) so as to hold the button (215) as shown in FIG. 16A, in readiness for actuation. Pressing the button (215) by the user causes the conical region (425) to fully enter the collar (430) due to deformation of the conical region and / or the lip (435). The upward face of the conical region (425) abuts against the lip (435), substantially locking the button (215) in the position shown in FIG. 16B and preventing the microneedles from being withdrawn from the skin (50).

[0209] The embodiments of FIGS. 17A - 17B include opposing spring - loaded posts (440) which are biased to assume the position shown in FIG. 17A. It should be noted that in FIG. 17A, the lower end of the post (440) extends beyond the lower surface of the device and thus suspends the device as a whole above the skin (50). Each post (440) has a vertical arm (445) extending inwardly therefrom. In this embodiment, the post (440) and the arm (445) are integrally formed, although having a frangible region (450) at the intersection which will bend or break when a force is applied to the post (440). Each arm (445) has a pivot point (455) and holds the microneedle carrier (300) in the retracted position against the bias of a helical spring (460) at its end. For actuation, the user pushes down on the housing (25), thereby pushing up on the post (440). Since the arm (445) is held at the pivot point (455), the frangible region (450) breaks and the end of the arm (440) drops, thereby releasing the body (300), as shown in FIG. 17B. Then, the spring (460) acts to push the body (300) downward so that the microneedles embed into the underlying skin.

[0210] Please refer to FIGS. 18A - 18B, which include a thin metal annular skirt (465) fixed to the body (300) and the housing (25). The skirt (465) is deliberately designed to bend under an axial force so as to quickly transition from a first state (FIG. 18A) to a second state (FIG. 18B). In the pre - actuation state (FIG. 18A), the central region of the skirt (465) is set upward so as to hold the body (300) and the microneedles above the skin (50). The user presses the button (215), causing the body (300) to start moving downward, which in turn causes the skirt (465) to snap downward (FIG. 18B). The body (300) moves quickly downward and embeds the microneedles into the skin. The snapping action of the skirt (465) does not allow the body (300) to move in any reverse direction, nor does it allow the body (300) to stop at any intermediate vertical level between those shown in FIGS. 18A and 18B. The buckling of the skirt can provide a tactile feedback to the user's finger through the rapid transition between the states. An audible feedback in the form of a "click" may also be generated by the buckling action.

[0211] Some embodiments of the device may require the upper region of the microneedles to be electrically insulated to prevent a conductive path from forming between the microneedles across the moist surface of the skin (which is different from the underlying biological fluid).

[0212] As another means of controlling humidity, an absorbent material can be positioned on the microneedle mounting portion and near the microneedle tips. In an embodiment of a device for sensing applications, the material is configured to absorb any excess fluid that may be created by inserting the microneedles into the skin to improve the patient experience and to ameliorate any problems that may result from fluid contact with other parts of the device, such as electronic circuitry or electrical contacts. In an embodiment of a device such as a fluid extraction application, the material acts as a wicking agent to transport fluid from the microneedle location to a desired final location on or outside of the device. In some embodiments, the absorbent material is in the form of a sheet. In embodiments where it is desired to prevent microneedle contamination or damage prior to insertion, the sheet includes holes through which the microneedles pass, where the holes are sized large enough to prevent the absorbent material from contacting the microneedles during the microneedle insertion process, but small enough to allow excess fluid exuding from the penetration point created by the microneedles to contact and be absorbed by the material. In other embodiments, such as when the device is intended for fluid extraction, there are no holes in the sheet of absorbent material, or the holes are sized such that the absorbent material contacts the microneedles during and after insertion to aid in its wicking action. In embodiments where there are no holes in the sheet, as part of the insertion process, the microneedles create holes as they pass through the sheet.

[0213] The device can be configured for and / or used in any suitable application where it is desired to embed the microneedles in a patient's skin for an extended period of time.

[0214] Such applications include electrochemical aptamer-based sensing, whereby 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 can be covalently or non-covalently bound to the microneedle, and the redox reporter causes the microneedle to transmit an electrical signal when the target analyte binds. The target analyte can be a drug or other exogenous substance, or an endogenous substance, such as a hormone or metabolite.

[0215] When the microneedles are used as electrodes to detect analytes present in skin layers, the device can include circuitry and components to electrically stimulate the electrodes and to receive, measure, and process the electrical signals generated by the electrical stimulation. According to this embodiment, the microneedles can include tips, shafts, and bases, where the electrical signals are generated at electrodes coated on or integrated with the microneedle surfaces, transmitted along the shafts of the microneedles to the bases of the microneedles, where electrical connections are made to the bases or shafts of the microneedles to transmit the electrical signals to the electronic circuitry and from the electrodes to the electronic circuitry. The electrodes can be formed near the tips of the microneedles, on at least a portion of the shafts of the microneedles and not near the tips of the microneedles, or both near the tips of the microneedles and on at least a portion of the shafts of the microneedles.

[0216] Microneedles can be connected to an electronic circuit by a variety of methods known in the art, such as soldering, wire wrapping, or sprung loaded pins. In one embodiment, the microneedles are mounted to pass through a dielectric material plate or block, where the connecting portion of the microneedles is positioned at or above the surface of the plate or block remote from the tips of the microneedles. Zebra strip connections can be used to connect the microneedles to the electronic circuit to facilitate a robust connection without the need to precisely align the zebra connector with the microneedle ends, at least in one dimension.

[0217] Another potentially useful application is the delivery of active substances into the skin. The substance may be retained primarily in the skin or may enter the systemic circulation. In such applications, the microneedles can be hollow and the substance is delivered through the lumen of the needles. Alternatively, the microneedles can be coated with the active substance such that the substance is released immediately into the biological fluid or is gradually released over an extended period of time. As a further alternative, the microneedles themselves can dissolve in the biological fluid and contain the active substance within their body such that the active substance is released when the microneedles dissolve. The active substance can be a pharmaceutical composition (e.g., small molecule, protein, peptide, or nucleic acid), or an immunologically active composition (e.g., a collection of proteins) used as a vaccine.

[0218] Another potential application is the delivery of an electric current to the skin for the purpose of muscle stimulation or for stimulating or inhibiting a patient's biological processes. Similarly, the device can be used to detect an electric current in a patient's skin, such as detecting nerve conduction.

[0219] In any of the above applications, the microneedles can be solid or hollow, as needed or desired.

[0220] The microneedle length can be selected according to the specific application. Generally, the microneedles need to extend at least below the stratum corneum. The depth of the stratum corneum varies depending on location, e.g., the stratum corneum on the soles of the feet is relatively thick and the stratum corneum on the back of the hand is relatively thin. Thus, the length of the microneedles extending beyond the housing can be adjusted according to the intended application site.

[0221] In some cases, the microneedles may need to extend below the stratum corneum and into the underlying epidermis, dermis, and even subcutaneous tissue (including the hypodermis). Again, the length of the microneedles extending beyond the device can be set accordingly.

[0222] One of ordinary skill will also understand that the microneedle length may need to be set according to the intended patient. For example, relatively short microneedles are typically required to achieve contact with the subcutaneous tissue of a neonatal patient, while for the same site, an adult patient will require longer microneedles.

[0223] In certain applications, it may be desirable for one microneedle to penetrate the skin deeper than another microneedle. Thus, the two microneedles can terminate at different distances from the skin surface, or at different distances from the microneedle mounting portion. In some embodiments, the two microneedles have different lengths. In other embodiments, the microneedles have the same length and the mounting portion is configured to axially displace one microneedle relative to the other. For example, the mounting portion can be multi-layered, having a first electrode extending from a first layer and a second electrode extending from a second layer.

[0224] For typical applications, the microneedles can extend outward from the device by a distance between about 10 μm and about 5000 μm. For many applications, a distance between about 500 μm and about 4000 μm will be useful.

[0225] Those of ordinary skill in the art will appreciate that the invention described herein is susceptible to further variations and modifications other than those specifically described.

[0226] For example, the movable arm can be moved by the user squeezing or pressing a flexible portion of the device housing, by actuation of a rotating lever, or by pushing the arm downward along an inclined sliding assembly.

[0227] The skin contact portion of the device has been depicted as being strictly flat on its underside (skin contact surface), however, in some embodiments, it can be curved to conform to 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) in order to conform to the surface of the body part.

[0228] The space through which the microneedles extend is typically shown as a hole, however, other types of spaces are also conceivable. In some embodiments, the space is not a hole, and there are embodiments of microneedles having a space that extends through the periphery of the skin contact portion.

[0229] It should be understood that the invention includes all of the foregoing variations and modifications as well as virtually further variations and modifications that fall within the spirit and scope of the invention.

[0230] Therefore, the spirit and scope of the invention are not limited by the foregoing embodiments, but should be understood in the broadest sense permitted by law.

Claims

1. An apparatus for applying one or more projections to contact the skin of a subject, the apparatus comprising: one or more projections, each of the one or more projections being 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 projections to extend therethrough; and a movable portion configured to move the one or more projections from a first position behind the skin contact surface to a second position projecting beyond the skin contact surface; wherein the apparatus is configured to maintain the one or more projections in a first state in which they cannot contact the skin of the subject until the user actuates the apparatus, the actuation causing or allowing the one or more projections to transition to a second state in which they are fully embedded in the skin, and the apparatus is further configured to (i) inhibit or prevent the one or more projections from transitioning back to the first state after the actuation, or (ii) require an intentional action by the user or another user to transition the one or more projections back to the first state after the actuation.

2. The apparatus according to claim 1, the apparatus comprising a maintaining portion configured to maintain contact between the skin contact surface and the skin during use.

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

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

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

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

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

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

9. The apparatus according to any one of claims 4 to 8, wherein the angular measure 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°.

10. The apparatus according to any one of claims 1 to 9, wherein the movable portion has a pivot portion, a hinge portion, a bend portion or a joint portion.

11. The apparatus according to any one of claims 1 to 10, wherein the movable portion is associated with a fixed portion.

12. The apparatus according to claim 11, wherein in use, the fixed portion is fixed and the movable portion is movable relative to the fixed portion.

13. The apparatus according to claim 11 or claim 12, wherein the fixed portion includes a part that allows the movable portion to pivot, hinge, bend or joint.

14. The device according to any one of claims 11 to 13, wherein the fixing part and the skin contact surface are in a fixed spaced relationship.

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

16. The device according to any one of claims 11 to 15, wherein the fixing part is generally lateral to the movable part.

17. The device according to any one of claims 1 to 16, the device further comprising a user-actuable release part configured to maintain the movable part in the first position until the user actuates the release part, at which time the movable part is released and allowed to move to the second position.

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

19. The device according to any one of claims 1 to 18, the device being configured such that the movement of the movable part from the first position to the second position requires a motive force originating from inside and / or outside the device.

20. The device according to claim 19, wherein the motive force inside the device originates from a spring, an elastically deformable member, a shape memory member or other biasing device; and the motive force outside the device originates from the user.

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

22. The device according to any one of claims 1 to 21, wherein the maintaining part is a dermatologically acceptable composition provided on or around the skin contact surface or comprises the dermatologically acceptable composition provided on or around the skin contact surface.

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

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

25. The device according to claim 24, wherein the maintaining part is selected from any one or more of the following: braces, strings, belts, clips, grips, ties, buttons, sleeves, stockings, socks, gloves, skullcaps, brimmed hats, underwear, vests, shirts, bras, blouses, trousers, scarves, rings, glasses and collars..

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

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

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

29. The device according to any one of claims 1 to 28, wherein the one or more protrusions have a sufficient length to be able to contact the epidermis, dermis or subcutaneous tissue of the subject.

30. The device according to any one of claims 1 to 29, wherein in use, the one or more protrusions are operative to: conduct an electric current to, from or through the skin, conduct sound waves to, from or through the skin, conduct light to, from or through the skin, conduct heat to, from or through the skin, sample a liquid or tissue from the skin, or deliver a bioactive substance to the skin, or introduce an analyte sensing substance to the skin.

31. The device according to any one of claims 1 to 30, wherein the one or more protrusions are each electrically conductive, and the device further comprises a circuit having an audible, visual or tactile indicator, the circuit being configured to actuate the indicator when the one or more protrusions contact a conductive liquid naturally present in the skin.

32. The device according to claim 31, wherein the circuit comprises at least two protrusions, and the circuit is configured to be completed by contacting the conductive liquid naturally present in the skin through the at least two protrusions so as to actuate the indicator.

33. The device according to claim 31, wherein the circuit comprises one protrusion and at least one conductive pad placed against the skin, and the circuit is configured to be completed by electrical communication between the protrusion and the pad with the conductive liquid naturally present in the skin so as to actuate the indicator.

34. The device according to any one of claims 1 to 33, the device comprising a housing sized such that when the device is applied to the skin and the movable part is in the second position and any part of each of the one or more protrusions protruding from the skin contact surface is embedded in the skin, most or substantially all of the housing extends no more than 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 above the skin.

35. The device according to any one of claims 1 to 34, wherein the device is configured to be used for a time 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.

36. The device according to any one of claims 1 to 35, the device being configured such that the one or more protrusions are non-detachable from the device, or non-detachable without the aid of tools.

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

38. The device according to claim 37, wherein the integral movable part and fixed part are made of an elastically deformable material.

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

40. The device according to any one of claims 17 to 39, wherein the movable part is biased towards the second position and maintained in the first position, and is resisted by the user-actuatable release part against the bias until the release part is actuated, at which time the movable part is released and allowed to move to the second position.

41. The device according to any one of claims 17 to 39, wherein the user-actuatable release part is a flange, the flange being configured to maintain the movable part in the first position, and the motive force provided by the user deforms the flange and / or the movable part so as to allow the movable part to be released from the flange and move to the second position.

42. The device according to any one of claims 1 to 41, wherein the movable part is hingedly associated with the skin contact part.

43. The device according to claim 42, wherein the hinge is provided at or towards the peripheral region of the movable part and the skin contact part.

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

45. The device according to claim 44, wherein the member can be removed by sliding substantially over the skin contact part.

46. The device according to claim 44 or claim 45, wherein the member is substantially wedge-shaped, and the device includes a hinge associating the movable part with the skin contact part, and the thin part of the wedge is provided proximal to the hinge and the thick part of the wedge is provided distal to the hinge.

47. The device according to any one of claims 44 to 46, wherein the release part is removable from the device and includes a gripping part to assist in manual removal.

48. The device according to any one of claims 1 to 47, the device being configured such that the transition of the one or more protrusions from the first state to the second state can be achieved by a single actuation action performed by the user on a device component or by the user moving a device component in a single direction.

49. The device according to claim 48, wherein the single actuation action or the movement in a single direction is selected from: pushing, pulling, pressing down, compressing, rotating, twisting, bending, squeezing, stretching, separating, breaking, joining, turning, reorienting, striking, tapping and shaking.

50. The apparatus according to any one of claims 1 to 49, the apparatus being configured such that once the transition begins, (i) the transition is irreversible for the user, or (ii) an intentional action of the user or another user is required.

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

52. The apparatus according to any one of claims 1 to 51, the apparatus being configured such that the transition is substantially instantaneous.

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

54. The apparatus according to any one of claims 1 to 53, wherein the one or more protrusions extend from a body that is acted upon during the transition.

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

56. The apparatus according to claim 55, the apparatus including a latching mechanism configured to prevent the one or more protrusions from moving from the first position until the user applies at least a threshold level of force to a component of the apparatus by an actuating action, and once the at least threshold level of force is applied, causing or allowing the one or more protrusions to transition to the second position in less than about 100 milliseconds, 90 milliseconds, 80 milliseconds, 70 milliseconds, 60 milliseconds, 50 milliseconds, 40 milliseconds, 30 milliseconds, 20 milliseconds, 10 milliseconds, 9 milliseconds, 8 milliseconds, 7 milliseconds, 6 milliseconds, 5 milliseconds, 4 milliseconds, 3 milliseconds, 2 milliseconds, 1 millisecond, or substantially instantaneously.

57. The apparatus according to claim 56, wherein the latching mechanism includes an elastically deformable structure that must deform to allow the one or more protrusions to move from the first position to the second position.

58. The apparatus according to claim 57, wherein the elastically deformable structure is associated with the one or more protrusions or with another component of the apparatus.

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

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

61. The device according to any one of claims 56 to 60, wherein the snap mechanism locks the one or more protrusions in the second position after actuation of the device.

62. The device according to any one of claims 56 to 61, the device comprising a body from which the one or more protrusions extend, wherein the snap mechanism comprises a portion extending from the body.

63. The device according to any one of claims 55 to 62, the device comprising a biasing means configured to maintain the one or more protrusions in the first position until actuation, or to move the one or more protrusions rapidly from the first position to the second position, or to maintain the one or more protrusions in the second position after actuation.

64. The device according to any one of claims 55 to 63, the device comprising one or more fasteners configured such that when the one or more protrusions move from the first position to the second position, the one or more fasteners are configured to allow the one or more protrusions to move towards the second position but to prevent the one or more protrusions from moving back towards the first position.

65. A method for applying a protrusion in contact with the skin of a subject, the method comprising the steps of: providing a device according to any one of claims 1 to 64, contacting the skin contact surface of the device with the skin, and causing or allowing the movable part to move from the first position to the second position along a non-linear path.

66. The method according to claim 65, wherein the device remains applied to the skin for a time 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.

Images