Microneedle application tools and methods

Abstract

A device or tool for applying microneedles to skin or other biological tissue is provided, the device including an applicator having an array of microneedles and a trigger mechanism operably connected to the applicator. The device is configured to apply the array of microneedles to the skin at a controlled rate, force, and angle. The device has no stored energy, and the trigger mechanism does not move the array of microneedles toward the skin until a threshold manual force is applied to the device.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 406,023, filed September 13, 2022, which is incorporated herein by reference.

[0002] Federally Sponsored Research and Development This invention was made with Government support under Prime Contract No. 7200AA20CA00016 awarded by the United States Agency for International Development. The Government has certain rights in this invention. [Background technology]

[0003] Microneedle array devices are applied to biological tissue, such as skin, for a variety of purposes, including, but not limited to, drug delivery (e.g., vaccination, administration of contraceptives) and diagnostics. The microneedles of the array generally must be applied to tissue with a specific force, speed, and angle of insertion to achieve the desired penetration of the microneedles into the tissue. Insufficient insertion force, insufficient speed, or a non-perpendicular insertion angle can undesirably result in incomplete or no insertion and / or unintentional breakage of the microneedle tip.

[0004] Conventional microneedle insertion may require user training to apply the correct force, speed, and angle of insertion, for example, to successfully apply the microneedle patch to a patient's skin. Alternatively or additionally, complex and / or expensive applicators or application systems may be required. For example, some conventional systems rely on stored energy within the microneedle patch or additional components coupled to the patch to provide the microneedle insertion force. The energy may be stored, for example, in the form of a spring or elastic material, or in the form of a battery that powers a mobile component that applies the patch to tissue. However, pre-stored energy may increase the risk of premature deployment of the microneedle array, resulting in material waste and / or improper application. Furthermore, conventional tools with pre-stored energy also require complex and specialized components that may be difficult and / or expensive to manufacture.

[0005] Self-administration of microneedle patches improves user compliance and has a positive impact on many pharmaceutical applications. However, given the above-mentioned importance that the microneedles must be properly applied to the skin or other tissue for accurate insertion, user error in self-administration must be minimized. Therefore, it is desirable to provide new and improved tools that facilitate reproducible and effective insertion, which can increase the success rate of microneedle application. It is desirable that such tools be relatively simple and inexpensive to manufacture and easy to use for self-administration. Summary of the Invention

[0006] In one aspect, a device or tool for applying microneedles to skin or other biological tissue is provided, the device comprising: an applicator including an array of microneedles; and a trigger mechanism operably connected to the applicator, the device configured to apply the array of microneedles to the skin at a controlled rate, force, and angle, the device having no stored energy, and the trigger mechanism not moving the array of microneedles toward the skin until a threshold manual force is applied to the device.

[0007] In certain embodiments, the device includes (i) a support structure from which the array of microneedles extends, and (ii) an applicator portion including a release mechanism, and a base portion configured to abut the skin or other biological tissue and hold the applicator portion in a pre-fired position with the microneedles facing the skin or other biological tissue at a distance from the surface of the skin or other biological tissue, the applicator portion configured to receive a manually applied force such that, when the force exceeds a predetermined threshold, the release mechanism triggers and releases the microneedles, together with at least a portion of the support structure, from the pre-fired position, thereby driving the microneedles along a guide path toward the skin or other biological tissue with a force and velocity effective to insert the microneedles into the skin or other biological tissue. The release mechanism may be configured to be triggered, for example, by multiple perforations in the support structure or mechanical breaking of a portion of the support structure at predetermined lines of weakness, or by deformation of a latch arrangement.

[0008] In another aspect, a method is provided, comprising: positioning a base of an applicator tool against a surface of a target tissue, with an array of microneedles extending from the applicator positioned within the base in a pre-fired position, the microneedles facing the surface of the target tissue at a distance of at least 5 mm; manually applying a force above a predetermined threshold to an upper surface of the applicator tool, causing a release mechanism connecting the applicator to the base to trigger and release the microneedles, along with at least a portion of the applicator, thereby causing the manually applied force to drive the microneedles along a guide path toward the tissue surface at a force and velocity effective to insert the microneedles into skin or other biological tissue, wherein triggering the release mechanism comprises either (i) mechanical disruption of a structure securing the applicator in the pre-fired position or (ii) deformation of a latching arrangement. The velocity may be about 1 m / s to about 15 m / s, preferably about 8 m / s, and the separation distance may be 5 mm to 3 cm, preferably about 15 mm.

[0009] The detailed description is set forth with reference to the accompanying drawings. The use of the same reference numbers may indicate similar or identical items. Various embodiments may utilize elements and / or components other than those shown in the drawings, and some elements and / or components may not be present in various embodiments. Elements and / or components are not necessarily drawn to scale. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a perspective view of a microneedle patch according to one embodiment of the present disclosure. [Figure 2A] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 2B] FIG. 2B is a perspective view of a base portion of the microneedle applicator tool of FIG. 2A in accordance with one or more embodiments of the present disclosure. [Figure 2C]FIG. 2B is an exploded perspective view of an applicator portion of the microneedle applicator tool of FIG. 2A in accordance with one or more embodiments of the present disclosure. [Figure 3A] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 3B] FIG. 3B is a perspective view of a base portion of the microneedle applicator tool of FIG. 3A in accordance with one or more embodiments of the present disclosure. [Figure 3C] FIG. 3B is an exploded perspective view of an application portion of the microneedle applicator tool of FIG. 3A in accordance with one or more embodiments of the present disclosure. [Figure 4A] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 4B] FIG. 4B is a perspective view of a base portion of the microneedle applicator tool of FIG. 4A in accordance with one or more embodiments of the present disclosure. [Figure 4C] FIG. 4B is a perspective view of an application portion of the microneedle applicator tool of FIG. 4A in accordance with one or more embodiments of the present disclosure. [Figure 5] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 6] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 7] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 8] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 9A] FIG. 1 is a perspective view of a microneedle applicator tool for simultaneous application of multiple microneedle patches according to one or more embodiments of the present disclosure. [Figure 9B] FIG. 1 is a bottom view of a microneedle applicator tool for simultaneous application of multiple microneedle patches in accordance with one or more embodiments of the present disclosure. [Figure 9C] FIG. 1 is a bottom view of a microneedle applicator tool for simultaneous application of multiple microneedle patches in accordance with one or more embodiments of the present disclosure. [Figure 9D] FIG. 1 is a bottom view of a microneedle applicator tool for simultaneous application of multiple microneedle patches in accordance with one or more embodiments of the present disclosure. [Figure 10] FIG. 1 is a perspective view of a microneedle applicator tool for sequential application of multiple microneedle patches according to one or more embodiments of the present disclosure. [Figure 11] FIG. 1 is a partially transparent perspective view of a microneedle applicator tool for sealing application according to one or more embodiments of the present disclosure. [Figure 12A] FIG. 1 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure. [Figure 12B] FIG. 12B is a side view of the microneedle applicator tool of FIG. 12A in accordance with one or more embodiments of the present disclosure. [Figure 13] 1 depicts the insertion of a microneedle patch using a microneedle applicator tool, according to one or more embodiments of the present disclosure. [Figure 14] 1 is a representative bright field image showing the insertion of a microneedle into an artificial skin model using a microneedle applicator tool, according to one or more embodiments of the present disclosure. [Figure 15] 1 is an optical coherence tomography (OCT) image showing the insertion of a microneedle into an artificial skin model using a microneedle applicator tool, according to one or more embodiments of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0011] Microneedle application devices, systems, and methods have been developed to more easily and effectively apply microneedles to skin or other tissue for medical or other purposes. Factors such as force, speed, acceleration, and the angle between the patch surface and the tissue all affect the interaction between the patch and the tissue, and importantly, whether the microneedles penetrate the tissue and how deeply they are inserted into the tissue. The applicator devices of the present disclosure are configured to allow a user to apply a sufficient and evenly distributed insertion force to the microneedle array, predictably achieving a desired insertion speed and angle (e.g., perpendicular to the skin surface). In general, the microneedle applicator tools disclosed herein store energy while the user actively applies force to the tool, and once the stored energy exceeds a threshold amount, release the energy in a manner effective to apply microneedles to the skin. If at any point the user stops applying force, any stored energy is released, and no additional energy is stored unless the user again applies force to the tool. That is, the tool is unable to store energy in the device while no force is being applied to the tool.

[0012] Unlike conventional microneedle applicator and patch designs, the energy for application of the microneedle application tools described herein is supplied solely by the force manually applied by the user to the application tool (e.g., by the user's thumb). In the tools described herein, applying an insertion force to the microneedle does not involve energy from a battery or a separate spring element. The device design may be beneficially easier and more cost-effective to manufacture and use, and may advantageously increase the reliability or effectiveness of self-administration. Advantageously, the microneedle application tools disclosed herein provide high-speed, high-impact application while ensuring a controlled (e.g., perpendicular) angle of insertion.

[0013] Successful application of microneedles to skin or other tissue generally depends on several parameters. First, sharpness of the microneedle tip is essential. The applicators of the present disclosure advantageously shield and protect the microneedle until the moment of insertion. Second, the microneedle should generally be inserted perpendicularly (although in some cases, non-perpendicular insertion may be desirable), and an appropriate amount of pressure should be uniformly distributed across the microneedle patch. An oblique insertion can generate uneven or insufficient pressure that can destroy the microneedle or hinder insertion and drug delivery. The applicators of the present disclosure advantageously facilitate uniform insertion of the microneedle at a controlled (e.g., perpendicular) angle.

[0014] An important part of the tools disclosed herein is having a space between the microneedle and the skin (before the applicator is fired) to allow for a high enough velocity for insertion of the microneedle to be achieved, for example a separation distance of at least 5 mm.

[0015] Applicator Device (Tool) In some embodiments, a device for applying microneedles to skin or other biological tissue is provided, the device including: (a) an applicator portion including (i) a support structure from which an array of microneedles extends, and (ii) a release mechanism; and (b) a base portion configured to abut the skin or other biological tissue and hold the applicator portion in a pre-fired position with the microneedles facing the skin or other biological tissue at a distance from the surface of the skin or other biological tissue, the applicator portion configured to receive a manually applied force such that when the force exceeds a predetermined threshold, the release mechanism triggers and releases the microneedles, together with at least a portion of the support structure, from the pre-fired position, thereby driving the microneedles along a guide path toward the skin or other biological tissue at a force and velocity effective to insert the microneedles into the skin or other biological tissue.

[0016] In some preferred embodiments, the device is configured to generate an effective speed for inserting the microneedle of 1 m / s to 15 m / s, preferably about 8 m / s. Lower speeds may allow the target tissue to elastically deform upon contact with the microneedle rather than being penetrated by it. The desired speed may be achieved by design factors including the spacing between the microneedle tip in the pre-firing position and the surface of the skin, and the force applied to the microneedle upon firing. For example, in some preferred embodiments, the predetermined threshold of manually applied force is 10 N to 70 N, preferably about 40 N.

[0017] Factors such as the geometry of the microneedles, the number of microneedles, and / or the density of the microneedles in the array can affect the optimal insertion force. The release mechanisms described herein can be modified to adjust the insertion force. For example, the insertion force can be adjusted by changing the material, thickness, and / or geometry of the structure of the release portion, which is designed to break by fracture or elastic or plastic deformation. For example, using a thinner or perforated material for the release portion can decrease the insertion force, while using a thicker material for the release portion can increase the insertion force.

[0018] Triggering the release mechanism releases energy temporarily stored in the applicator device, which is transferred from the user applying force to the applicator device. The released energy is effective to fire the applicator portion and insert the array of microneedles into the skin (or other biological tissue) without any additional energy source. That is, energy is stored only while the user is applying force to the applicator device.

[0019] The base portion may include a stabilizing portion configured to be positioned against the patient's skin so that the guide path is perpendicular to the surface of the skin at the target site of microneedle insertion. The base portion may include one or more outer walls defining an opening through which the microneedle, along with at least a portion of the support structure, is configured to move along the guide path. In some embodiments, the walls of the base portion include guide rails along which the applicator portion can translate. For example, the applicator portion may include slots that mate and engage with the guide rails. In some other embodiments, the applicator portion has a guide rail and the base portion has a corresponding slot. In some embodiments, the opening defined by the one or more walls of the base portion is cylindrical, and the applicator portion includes an elongated cylindrical body configured to translate within the opening.

[0020] In some embodiments, the release mechanism is integral with the support structure.

[0021] The release mechanism can be configured to be triggered by mechanical failure. In some embodiments, the release mechanism is configured to be triggered by mechanical destruction of a portion of the support structure. The support structure can include a polymer film and can include a plurality of perforations or predetermined lines of weakness, or a combination thereof.

[0022] In some embodiments, the release mechanism comprises a tape or other thin film structure designed to break and release the energy stored within it when the force applied by the user exceeds the material's fracture strength (its ability to resist crack-based failure under an applied load). For example, the applied force can deform the structure beyond its elastic limit, causing it to break and release the energy stored within. In some embodiments, the structure includes weakened regions for more precise control of the insertion force and speed of the microneedle patch. The weakened regions can be formed by reducing the thickness of the structure in specific areas and / or by including perforations or other defects to ensure the structure breaks in desired areas for uniform release.

[0023] The release mechanism can be configured to be triggered by elastic or plastic deformation beyond a certain point, resulting in momentary displacement and release of stored energy within the applicator portion without destroying the structural components holding the applicator portion in the pre-fired position. In some embodiments, the release mechanism is configured to be triggered by elastic deformation of a latching structure. For example, the latching structure can include a lip (e.g., a ring, tab, other protrusion, etc.) on the applicator portion that interferes with a ledge (e.g., another ring, tab, other protrusion, etc.) on the wall of the base portion in the pre-fired position.

[0024] In some embodiments, the release mechanism is separate from the support structure. For example, the applicator portion can include an elongate body having an upper end portion configured to receive a manually applied force and a lower end portion including an array of microneedles, with the release mechanism disposed between the upper and lower end portions.

[0025] Microneedle Arrays and Patches Essentially any microneedle array or microneedle patch can be used with the applicator of the present disclosure. In certain embodiments, the microneedles contain a drug of interest to be administered to the skin or other biological tissue. For example, the microneedle array of the present disclosure can be a patch containing dissolving microneedles for administering a drug, as known in the art.

[0026] An example of a microneedle patch having an array of microneedles is depicted in FIG. 1. The microneedle patch 100 includes a backing layer 110 from which extends a 10 x 10 array of microneedles 120. The phrases "backing layer" and "base substrate" or "substrate" are used interchangeably herein. Each microneedle 120 has a proximal end 122 attached to the backing layer 110, either directly or indirectly via one or more proximal portions 124, and a distal tip 126 that is sharp and effective for penetrating biological tissue. The microneedles 120 have tapered sidewalls 128 between the proximal and distal ends 122, 126 of the microneedles 120.

[0027] A wide range of drugs can be formulated for delivery to biological tissues using microneedle patches.As used herein, the term "drug" refers to preventive, therapeutic, or diagnostic agents useful for medical applications, as well as drugs used in cosmetics, cosmeceuticals, tattoos, or other non-medical applications.It can be any suitable active pharmaceutical ingredient or allergen.The drug can be a hormone, such as a contraceptive hormone, or a vaccine.Examples of vaccines include vaccines against infectious diseases, therapeutic vaccines against cancer, neurological disorders, allergies, and smoking cessation or other addictions.

[0028] In some embodiments, the structure and composition of useful microneedle arrays with applicators of the present disclosure are described in U.S. Pat. Nos. 10,265,511, 10,828,478, 10,940,301, 11,730,937, U.S. Patent Application Publication No. 2022 / 0401715, and WO 2023 / 164306, which are incorporated herein by reference.

[0029] Particular applicator devices, systems, and methods 2A-13 illustrate embodiments of microneedle application tools and systems, and methods of use thereof. Generally, a microneedle application tool includes a base portion and an applicator portion (including an array of microneedles) operably connected thereto. The tool includes a release mechanism configured to fail upon application of sufficient manual downward force to the applicator portion, such that failure launches the microneedles toward the patient's skin using only manually applied force. The microneedles are fired such that the microneedles penetrate the patient's skin at a desired, predetermined velocity. As used herein, "failure" refers to the destruction or deformation of the release mechanism.

[0030] 2A-2C show a microneedle application tool 200 including a base portion 202 and an applicator portion 204 that can be releasably attached to the base portion. The applicator portion 204 includes a top portion 206, an ejection portion 208, and a backing portion 210. Figure 2A shows the tool 200 with the applicator portion in a pre-fired position with the microneedles facing the tissue surface at a distance from the tissue surface.

[0031] The base portion 202 is configured to stabilize and orient the microneedle application tool 200 in biological tissue, such as a patient's skin, during application of an array of microneedles. A foot 212 of the base portion 202, which is intended to be placed against the surface of the tissue (not shown), is shaped and dimensioned to provide the desired stabilization and orientation. The foot 212 has a generally square shape, but may have any other suitable shape. The foot 212 has a bottom opening 214 through which the microneedles of the applicator portion 204 are guided for insertion into the tissue.

[0032] In some embodiments, at least a portion (i.e., one side) of the base portion 202 is open to facilitate operation of the applicator tool and to accommodate anatomical variability among potential device users. For example, by leaving a portion of the tool open, a user can easily orient and grasp the tool as needed to apply the necessary pressure to the applicator portion. In some cases, for example, the thumb can be more easily inserted into the tool while the user's fingers can support the bottom of the base near the application area.

[0033] The base portion 202 has a wall 216 that extends upward from the foot 212 of the base 202 to form a U-shape and defines a side opening 218 within which a user can place their thumb. The side opening 218 allows the thumb (i.e., the widest finger capable of generating the most force) to seat inside the tool 200 and move freely until the array of microneedles is applied to the skin. The side opening 218 can also allow the user to maintain downward pressure on the applicator 204 while it passes through the interior cavity 220 of the base without generating a rebound force.

[0034] The base portion 202 has an upper surface 222 configured to hold at least a portion of the applicator portion 204 in a pre-fired position in which the microneedles face the tissue surface at a distance from the tissue surface. The upper surface 222 of the base portion 202 has ledges 224 on either side of the base 202 configured to hold at least a portion of the applicator portion 204, for example, along opposing edge regions of the portion of the applicator portion. The ledges 224 are configured to hold a portion of the ejection portion 208 of the applicator 204, as shown in FIG. 2A .

[0035] The base portion 202 also includes an elongated slot 226 perpendicular to the bottom surface of the foot. The slot 226 is located on the side of the wall 216 facing the cavity 220. Each wall 216 may have at least one slot 226. In the embodiment shown in FIGS. 2A-2C, one wall has exactly three slots and two walls have exactly two slots. The slots 226 are configured to receive corresponding guide rails 228 extending from the side of the applicator portion 204. The guide rails 228 are configured to slide vertically within the slots 226 so that the applicator portion 204 (and the array of microneedles extending therefrom) remains perpendicular to the tissue surface as the applicator portion translates toward the tissue surface. The slots and guide rails are dimensioned to limit tilt and / or wobble of the applicator portion within the base during microneedle insertion, making the insertion process more accurate and reproducible. The slots 226 each include a T-shaped channel, although other channel shapes are possible. However, it is preferred to include a channel shape that mates with the guide rail 228 to allow movement of the guide rail (and therefore movement of the applicator portion) along only one axis relative to the base portion. It is understood that the slot and guide rail features can be interchanged such that the base portion has the guide rail and the applicator portion has the slot.

[0036] 2A, the applicator portion 204 is generally sized and shaped to be disposed within and translate through the cavity 220 of the base portion. However, a portion of the applicator portion's discharge portion 208 extends laterally beyond the cavity 220 and contacts a ledge 224 of the base portion 202. This portion of the applicator portion's discharge portion 208 can be glued or otherwise attached to the ledge 224 of the base portion 202, especially if the discharge portion is a highly flexible material such as a tape or polymer film.

[0037] The applicator portion 204 can include a top portion 206, a release portion 208, and a backing portion 210. An array of microneedles 230 extends from a bottom surface 232 of the backing portion 210. A microneedle array, e.g., a microneedle patch, can be releasably attached to the bottom surface 232 of the backing portion 210. The top portion 206 includes a user force application area 242 disposed around the center of the top surface 234 of the top portion 206, which indicates the area where the user should apply manual pressure, e.g., with their thumb, to initiate microneedle application. The user should apply a downward force to the center of the top portion 206 to ensure that the release portion 208 breaks evenly and the microneedle array is evenly launched toward the surface of the skin. While the user force application area 242 is depicted as circular, it will be understood that other suitable shapes may be employed. In the illustrated embodiment, the user force application area 242 includes an anti-slip feature, which in this embodiment includes a plurality of nodules 244. In some other embodiments, the user force application area includes a recessed area and / or includes ridges or texture to facilitate a user's grip. In some embodiments, application area 242 may be slightly elevated from top surface 234 of top portion 206 to provide additional user guidance, for example, in the form of a button (e.g., approximately 5 mm in height). Such non-slip features may also help prevent the user's thumb from slipping during use, thereby preventing stuttering or wobbling that could cause damaging application.

[0038] The applicator portion 204 is ejected from its pre-fired position shown in FIG. 2A upon failure within the ejection portion 208. For example, the ejection portion 208 may include perforations 236 that indicate the area where the ejection portion 208 is configured to fail, as shown in FIG. 2C. The perforations 236 may help ensure that the ejection portion 208 fails in the designated area. That is, the ejection portion 208 should fail along the perforations 236, such that the central portion 238 of the ejection portion 208 remains with the remainder of the applicator 204 during insertion, while the edge regions 240 of the ejection portion 208 remain secured to the base 202. In other words, the fact that the edge regions 240 extend beyond the sides of the top 206 and backing portion 210 and are directly attached to the base 202 facilitates failure of the ejection portion along the perforations 236.

[0039] The microneedle application tool 200 can be constructed of any suitable material. In some embodiments, the base 202 and the top 206 and backing portion 210 of the applicator 204 are constructed of the same material. In some embodiments, the base 202, top 206, and backing portion 210 are constructed of two or more different materials. For example, the base 202, top 206, and / or backing portion 210 can be constructed of plastic, metal, ceramic, glass, or any combination thereof. In some embodiments, the base 202, top 206, and / or backing 210 can be constructed of recyclable and / or biodegradable materials, such as recyclable and / or biodegradable plastics.

[0040] In some embodiments, the applicator of the microneedle application tool differs from that described with respect to Figures 2A-2C. For example, in some embodiments, the release portion is not separate from the top and / or backing portion of the applicator. For example, the release mechanism may be incorporated into the top or backing portion of the applicator. In some embodiments, the applicator is a single piece that includes the release mechanism. In some embodiments, the applicator may be formed with the base of the microneedle application tool.

[0041] 3A-3C show a microneedle applicator tool 300 having a base portion 302 and an applicator portion 304. The applicator portion 304 includes a top portion 306 and a backing portion 308. Figure 3A shows the tool 300 with the applicator portion in a pre-fired position with the microneedles facing the tissue surface at a distance from the tissue surface.

[0042] 2A-2C. For example, the foot 312 of the base portion 302 is substantially square and defines a bottom opening 314 through which the microneedles of the applicator portion 304 can pass to penetrate the skin. The base portion 302 has three walls 316 that extend upwardly from the foot 312 of the base portion 302 to form a U-shape, thereby defining side openings 318 into which a user can place their thumbs to hold the applicator portion 304 while passing it through an interior cavity 320 defined by the walls 316.

[0043] Base portion 302 also includes a top surface 322 having an opening configured to receive applicator portion 304. Top surface 322 includes ledges 324 on opposing walls 316 of base portion 302, which are configured to receive opposing sides of backing portion 308. In the illustrated embodiment, each ledge 324 has an upward protrusion 323 configured to pass through an opening 337 in backing portion 308 to secure backing portion 308 to base portion 302.

[0044] Base portion 302 includes slots 326 disposed on the sides of walls 316 facing cavity 320. Each wall 316 may have at least one slot 326. In the embodiment shown in FIGS. 3A-3C, each wall has exactly three slots. Slots 226 are configured to receive corresponding guide rails 328 extending from side to side of top portion 306. Guide rails 328 are configured to slide vertically within slots 326.

[0045] The applicator portion 304 includes a top portion 306 and a backing portion 308 having an array of microneedles (not shown) extending from a bottom surface 332 thereof.

[0046] 3C , the backing portion 308 includes weakened attachment points 333 connecting the side loops 335 and a central portion 338 of the backing portion 308. The backing portion 308 is configured to break at the attachment points 333, so that the central portion 338 of the backing portion 308, which holds the microneedle, remains with the applicator portion 304 during insertion, while the side loops 335 remain secured to the ledge 324 of the base portion 302. The top surface 334 of the top portion 306, although not shown, can include a user force application area including an anti-slip feature as described above for the applicator tool 200.

[0047] Figures 4A-4C show another embodiment of a microneedle applicator tool 400 having a base portion 402 and an applicator portion 404. The applicator tool 400 differs from that shown in Figures 2A-3C in that the applicator portion 404 is a single component rather than an assembly of a top and an ejection portion / backing portion.

[0048] 2A-2C , the base portion 402 has a foot 412 that is substantially square and defines a bottom opening 414 through which an array of microneedles extending from the applicator portion 404 can pass to apply the microneedles to the skin. The base portion 402 has three walls 416 that extend upward from the foot 412 to form a U-shape and define side openings 418 through which a user can place their thumbs to apply pressure to the applicator 404 while it passes through an interior cavity 420 defined by the walls 416 of the base portion 402.

[0049] The base 402 also has a side slot 411 below the top surface 422 of the base portion 402. The applicator portion can be slid horizontally into the side slot 411 to place the applicator portion in its pre-fire position.

[0050] The base 402 also includes an elongated slot 426 that is elongated in a direction perpendicular to the bottom surface of the foot. The slot 426 is disposed on the side of the wall 416 that faces the cavity 420. The slot 426 is configured to receive a corresponding guide rail 428 that extends from the side of the applicator portion 404. The guide rail 428 is configured to slide vertically within the slot 426 such that the applicator portion 404 (and the array of microneedles extending therefrom) remains perpendicular to the surface of the tissue as the applicator portion 404 translates toward the surface of the tissue.

[0051] A microneedle array (not shown) is attached to the bottom surface 432 of the applicator portion 404. As shown in FIG. 4C , the applicator portion 404 has a central body region 438 disposed between two edge regions 440 and includes a line of perforations 436 between the body portion 438 and the edge region 430. The body portion 438 is configured to be sufficiently rigid to distribute an insertion force evenly across the microneedle array, for example, to facilitate uniform insertion of the microneedles. The perforations 436 facilitate mechanical breakage at a desired location between the body portion 438 and the edge region 440 when sufficient force is applied to the top surface 434 of the body portion 438. In some other embodiments, the applicator portion may include other features, such as weakened portions / regions, instead of or in addition to perforations to control the breakage force and location, generating a desired insertion speed and force driving the microneedles.

[0052] Under sufficient load, the applicator portion 404 is designed to break along the perforations 436 so that the main portion 438 is ejected toward the tissue surface along with the microneedle to insert the microneedle, while the edge region 440 remains positioned within the side slot 411.

[0053] FIG. 5 illustrates yet another embodiment of a microneedle applicator tool 500. In this tool, a base portion 502 and an applicator portion 504 are formed together as a unitary piece, with the applicator portion in a pre-fired position. The base portion 502 is similar to the base portion 202 described above with reference to FIGS. 2A-2C. The foot portion 512 is substantially square and defines a bottom opening 520 through which a microneedle 530 extending from a bottom surface 532 of the applicator portion 504 can pass to apply the microneedle to the skin. The base 502 has three walls 516 extending upward from the foot portion 512, forming a U-shaped side opening 518 through which a user can place their thumb to apply pressure to a top surface 534 of the applicator portion 504 while the applicator portion 504 passes through an interior cavity 514 defined by the walls 516 of the base portion 502. The interior of wall 516 includes a plurality of slots 526 that open into cavity 514. Slots 526 are configured to receive corresponding guide rails 528 extending from the sides of applicator portion 504. Guide rails 528 are configured to slide vertically within slots 526 such that applicator portion 504 (and the array of microneedles extending therefrom) remains perpendicular to the surface of the tissue as applicator portion 504 translates toward the surface of the tissue.

[0054] At the top side 522 of the base portion, the applicator portion 504 and the base portion are connected to one another via two weakened areas 531 that contain a line of perforations 536. When a sufficient downward load is applied to the top surface 534, the applicator portion 504 and the base portion 502 separate (break) along the perforations 536, and the applicator portion and the microneedles are launched towards the surface of the tissue for insertion of the microneedles.

[0055] Although the microneedle application tools described herein are generally configured to apply microneedles to relatively flat areas of skin on the extremities or other body parts of a human patient, the tools can be readily adapted to other biological tissues that may or may not be substantially flat. In some other embodiments, it may be useful to apply the microneedle patch to thin, flexible tissue that can be held in a relatively flat orientation to receive the microneedle array. For example, in veterinary or animal husbandry applications, it may be useful to apply the microneedle patch to the ears of dogs, cats, cows, pigs, sheep, etc. for various treatment, vaccination, identification, or tracking purposes.

[0056] Thus, the microneedle application tools described above may be adapted to further include a connected or separate tissue support structure configured to support and orient the planar tissue while the microneedle patch is being applied.

[0057] Figure 6 shows a microneedle application tool 600 having a base 602, an applicator 604, and a tissue support portion 606. In general, the base 602 and the applicator 604 may be similar in structure and function to the microneedle application tools described above with respect to Figures 2A-5.

[0058] The base 602 is similar to the base portion 302 of FIGS. 3A-3C. The base 602 has an upper surface 608 configured to hold at least a portion of the applicator 604 thereon. The upper surface 608 of the base 602 includes ledges 610 on either side of the base 602 configured to hold the applicator 604. The ledges 610 have upwardly protruding protrusions 611 to further secure the applicator 604 to the base 602. The base 602 may also include guide rails (not shown), which may be similar to those described with respect to any of the previous embodiments. The base 602 also includes hooks 612 for attaching a strap 614 to the application tool 600. The strap 614 may be an elastic strap and may help further stabilize the application tool 600 in a user's hand during its use. For example, the user can place their thumb (or other finger being used to depress the applicator 604) between the strap 614 and the applicator 604 to help secure the application tool 600 to the user.

[0059] 3A-3C . Applicator 604 includes a top portion 616 and a backing portion 618. An array of microneedles (not shown) can be positioned on the underside of backing portion 618, and when sufficient downward force is applied by a user to top side 620 of top portion 616, applicator 604 is released from base 602 and the microneedles are applied to the skin.

[0060] In use, the base 602 and applicator 604 are positioned on one side of the target tissue (e.g., the skin of an animal's ear), and the tissue support portion 606 is positioned on the opposite side of the target tissue. The tissue support portion 606 includes a substantially flat platform 622 configured to contact the skin and a handle 624 configured for a user to hold and control the support portion. Thus, the platform 622 is positioned opposite the base 602 at the target tissue and effectively supports the base 602 thereon to ensure proper insertion of the microneedles. In the illustrated embodiment, the handle 624 has a ring-like shape, allowing the support portion to be worn on a user's finger to facilitate easy use of the application tool 600. The ring may be adjustable to accommodate different fingers and / or different users.

[0061] FIG. 7 shows another embodiment of a microneedle application tool 700 having a base 702, an applicator 704, and a tissue support portion 706. The base 702 and applicator 704 may be similar to the base portion 502 and applicator portion 504, respectively, of FIG. 5. The base 702 and applicator 704 may be formed as a single piece, where the applicator 704 is attached near a top surface 708 of the base 702 via one or more weakened regions configured to break upon application of a sufficient amount of force to the applicator 704. The base 702 and tissue support portion 706 are connected by a connecting portion 710 that forms a gap 712 between the bottom of the base 702 and a platform 714 of the tissue support portion 706. To apply microneedles using the microneedle application tool 700, tissue is placed in the gap 712 so as to contact at least the platform 714, and in some embodiments, the bottom of the base 702 and the platform 714. That is, the tissue may not initially contact the bottom of the base 702, but may contact the bottom of the applicator 704 as the applicator 704 moves toward the tissue. Accordingly, the connecting portion 712 of the tool 700 is preferably flexible or otherwise adjustable so that it can be configured to vary the gap height within a useful range of tissue thicknesses, allowing the tissue to reliably contact the foot of the base while still being supported by the tissue support portion 706. The tissue support portion also includes a handle 716, which may be a ring as described with respect to FIG. 6.

[0062] 8 shows another embodiment of a microneedle application tool 800, the tool 800 having a base 802, an applicator 804, and a tissue support portion 806. The base 802 has an arch shape, and the applicator 802 has two legs 808 defining a bottom gap 810 therebetween for the applicator 804 to translate a microneedle array (not shown) toward and into tissue. The applicator 804 is positioned at an intermediate position 812 between the legs 808 and the top of the arch 814. The applicator 804 includes a weakened portion (not shown) where the applicator 804 is attached to the base 802. The weakened portion is configured to mechanically break to apply the array of microneedles to tissue, as described above in other embodiments.

[0063] An upper opening 816 is defined between the applicator 804 and the arch 814, where a user can place their thumb (or another finger) to apply insertion force to the applicator 804. The base 802 includes a hook 818 above the applicator 804, which can be used to secure a strap (not shown) to the base 802 to accommodate users with different anatomical characteristics.

[0064] In use, the base 802 and applicator 804 are placed on one side of the target tissue (e.g., the skin of an animal's ear), and the tissue support portion 806 is placed on the opposite side of the target tissue. The tissue support portion 806 includes a substantially flat platform 820 configured to contact the target tissue and a handle 822 extending below the platform for a user to hold and control the support portion. The platform 820 may be positioned opposite the base 802 at the tissue to effectively support the base 802 thereon to ensure proper insertion of the microneedles. In some embodiments, the top of the platform 820 is covered or coated with a material to prevent tissue slippage and / or to provide additional comfort while the microneedles are being applied.

[0065] The microneedle applicator tool may be configured to apply multiple microneedle patches with a single applicator. In some embodiments, the microneedle applicator tool is configured to apply multiple microneedle patches simultaneously. In some embodiments, the microneedle applicator tool is configured to apply multiple microneedle patches sequentially. In some such embodiments, the applicator includes a tip, an emission portion, and a backing portion. In some other such embodiments, the applicator includes a tip and a backing portion. In yet some other such embodiments, the applicator is a single piece. In yet some other such embodiments, the applicator is formed as a single piece with a base.

[0066] 9A-9C show a microneedle application tool 900 configured to simultaneously apply two microneedle patches. The microneedle application tool 900 comprises a base 902 and an applicator 904. The base 902 and applicator 904 may be similar to the base and applicator portions described with respect to any of FIGS. 2A-5C.

[0067] 9B, the bottom surface 906 of the applicator 904 is separated into multiple separate blocks 908a and 908b with microneedle arrays 914a and 914b attached, respectively. The blocks 908a, 908b are separated by gaps 910 configured to receive corresponding stops 912 on the base 902 when the applicator is fired / microneedles are inserted. The stops 912 can also provide additional stability to the base 902, as the base 902 can have a larger profile to accommodate multiple microneedle patches.

[0068] The microneedle application tool 900 is configured to dispense two separate microneedle arrays. The applicator 904 has two blocks 908a and 908b and is configured to dispense two microneedle arrays 914a and 914b simultaneously. The applicator tool can be adapted to dispense other numbers of microneedle patches and arrays, such as 3, 4, 5, 6, 7, 8, 9, or 10 (or more) microneedle arrays. For example, Figure 9C shows an applicator 950 having four blocks 958 and configured to dispense four microneedle arrays 954 simultaneously.

[0069] Figure 10 shows one embodiment of a microneedle application tool 1000 configured to apply an array of multiple microneedles in series. The microneedle application tool 1000 includes a base 1002 having multiple applicators 1004. The base 1002 and applicators 1004 may be similar to the base and applicator portions described with respect to any of Figures 2A-5C.

[0070] The base 1002 includes a plurality of openings 1006 for receiving applicators 1004 therein. Adjacent openings may be separated by legs 1008 to maintain separation between the microneedle arrays.

[0071] The base 1002 can have any suitable number of openings depending on the number of microneedle arrays to be administered. For example, the microneedle application tool 1000 can be configured to apply 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more microneedle arrays. In the embodiment shown in Figure 10, the microneedle application tool 1000 has four applicators 1004.

[0072] In certain embodiments, the microneedle application tool may be configured to insert the array of microneedles into the skin and apply a shear force, for example, to facilitate separation of the microneedles from the patch substrate.

[0073] FIG. 11 shows a microneedle application tool 1100 for inserting a microneedle array with shear force, the application tool 1100 including a base 1102 and an applicator 1104. The base 1102 and applicator 1104 can be similar to those described with respect to any of FIGS. 2A-5C. In some embodiments, the applicator includes a top portion, an ejection portion, and a backing portion. In some embodiments, the applicator includes a top portion and a backing portion. In some embodiments, the applicator is a single piece. In some embodiments, the applicator is formed as a single piece with the base. The base 1102 is configured to support the applicator 1104, which has a top portion 1106 and a bottom portion 1108 connected by an inclined guide rail 1110. The base 1102 can also define a gap 1112 between the bottom portion 1108 and the skin, allowing the applicator 1104 to pass through the gap 1112 to apply the microneedles to the skin. The top 1106 of the applicator 1104 includes a predetermined weakened portion configured to break upon application of a sufficient amount of downward force to the applicator 1104. When the weakened portion breaks, the guide rails 1110 may allow the applicator to move along the y-axis and then along the x-axis to apply the microneedles to the skin (e.g., an L-shaped motion). That is, the applicator 1104 first moves vertically to insert the microneedles vertically into the tissue, and then begins to move horizontally to apply a shear force to the microneedles, thereby separating them from the backing.

[0074] As shown in FIGS. 12A-12B , a microneedle application tool 1200 for applying an array of microneedles to biological tissue includes a base 1202 and an applicator 1204, where the base 1202 includes a guide portion 1206, a stabilizing portion 1208, and a microneedle support portion 1210 disposed therebetween. The base 1202, and more specifically the stabilizing portion 1208, are configured to stabilize and orient the microneedle application tool 1200 in biological tissue, such as a patient's skin, during application of the array of microneedles. The foot 1212 of the stabilizing portion 1208 of the base 1202 may be substantially circular and define a bottom opening (not shown) through which the applicator 1204 can pass to apply the microneedles to the skin. While the foot 1212 of the base 1202 is shown as circular, it will be understood that other geometric shapes are possible and are contemplated by the present disclosure. For example, the foot of the base can have any shape, such as a square or rectangular shape.

[0075] The stabilizing portion 1208 can have at least one protrusion 1214 extending upward at an angle from the foot 1212 and extending upward from a top surface 1216 of the stabilizing portion 1208. The protrusion 1214 can be configured to receive and retain the microneedle support portion 1210 through a reciprocal slot 1218 therein. The protrusion 1214 can also define a space therein configured to receive the guide portion 1206 of the base 1202 such that the guide portion 1206 can rest on top of the microneedle support portion 1210.

[0076] The guide portion 1206 is generally cylindrical, with a bottom 1220 positioned above the stabilizing portion 1208 and the microneedle support portion 1210, a cylindrical central portion 1222 extending upward from the bottom 1220, and side arms 1224 positioned above the central portion 1222. The side arms 1224 can assist a user in holding the applicator tool 1200 during use. The central portion 1222 includes a window 1226 through which the applicator 1204 can be viewed. The window 1226 also advantageously allows air between the applicator 1204 and the guide portion 1206 to escape as the applicator 1204 moves within the guide 1206, mitigating any negative effects that compressed air may have on application force and / or speed. During use, the applicator 1204 is configured to apply an array of microneedles to a patient's skin. The applicator 1204 may include an elongate body 1228 slidably disposed within the guide portion 1206 and a stopper 1230 configured to abut the side arm 1224 of the guide portion 1206 when the applicator 1204 successfully applies the array of microneedles to the skin.

[0077] The applicator 1204 includes a lip 1232 disposed about the elongate body 1228. The lip 1232 is configured to rest on or within a reciprocal ledge 1234 of the guide portion 1206, which defines an opening through which the applicator 1204 is received. When a downward force is applied to the stopper 1230, the lip 1232 can begin to deform the ledge 1234. Continued force can cause the lip 1232 to deform to a point where the ledge 1234 releases the lip 1232, thereby releasing the applicator 1204 and applying the microneedles to the skin. In some alternative embodiments, the lip, rather than the ledge, may undergo a trigger release upon deformation. In various embodiments, the lip and ledge deformations can be elastic, plastic, or a combination thereof.

[0078] How to apply An exemplary method of using the microneedle tools and systems disclosed herein is shown in FIG. 13. Generally, the method includes placing an application tool having a base and an applicator portion against a target tissue and applying an effective amount of downward force to the applicator portion to release the applicator from the base. As the applicator is released from the base, it moves toward the target tissue to achieve a velocity sufficient to apply the microneedles to the target tissue. Factors affecting velocity include the amount of energy stored in the tool from the force applied by the user before release of the applicator is triggered and the distance between the microneedles and the tissue surface before the applicator is released. In certain embodiments, the applicator is designed to generate a selected velocity profile to provide maximum velocity during contact / insertion of the microneedles.

[0079] 13, the microneedle application tool 1300 has a base 1302 and an applicator 1304, which includes a top portion 1306, an emission portion 1308, and a backing portion 1310 to which a microneedle array 1312 is attached. As shown in step (a), the base 1302 of the microneedle application tool 1300 is placed on the surface 1314 of the target tissue such that the longitudinal axes of the microneedles 1312 are substantially perpendicular to the tissue surface 1314 and the tips of the microneedles are pointed toward and away from the tissue surface.

[0080] After the microneedle application tool 1300 is properly positioned on the surface 1314 of the target tissue, the user manually applies force to the top 1306 of the applicator 1304 until the ejection portion 1308 breaks, ejecting the applicator 1304 from its pre-fired position within the base. The ejection portion 1308 is configured to mechanically break in response to sufficient user-applied force. For example, the ejection portion 1308 can be formed from a material that can stretch or strain to a threshold point that results in the material's failure (i.e., fracture). In some embodiments, the force required to break the ejection portion 1308 is between about 10 N and about 70 N, e.g., between about 10 N and about 60 N, between about 20 N and about 50 N, between about 30 N and about 50 N, or about 40 N.

[0081] When the applicator 1304 is released from the base 1302, it moves downward to the surface of the tissue, inserting the microneedle array 1312 vertically into the tissue 1314. The distance the applicator 1304 moves depends on the height of the base 1302 and the height of the microneedle array 1312 above the tissue 1314 when the application tool 1300 is assembled prior to use. In some embodiments, this height is between about 5 mm and about 3 cm, e.g., between about 10 mm and about 20 cm, between about 5 mm and about 15 mm, or about 15 mm.

[0082] The speed at which the applicator 1304 moves towards the tissue 1314 may be proportional to the force applied to the applicator 1304 to induce breakage of the releasing portion 1308 and / or the distance the applicator 1304 moves to apply the microneedle array 1312 to the tissue. For example, a greater breakage force may result in the microneedles 1312 being applied at a faster insertion speed. In some embodiments, the speed of the microneedle array 1312 is between about 1 m / s and about 15 m / s, e.g., between about 2 m / s and about 12 m / s, between about 3 m / s and about 10 m / s, between about 4 m / s and about 9 m / s, between about 5 m / s and about 8 m / s, or about 8 m / s. [Example]

[0083] The present invention can be further understood with reference to the following non-limiting examples.

[0084] Example 1. Preparation of a microneedle patch Microneedle arrays were fabricated using a solution casting method. 90 μL of an aqueous solution consisting of 18% PVA and 18% sucrose (w / w) was cast into a microneedle mold and allowed to dry at room temperature for 24 hours. Once demolded, the microneedle (array) patches were stored in a desiccator for at least 24 hours for further drying.

[0085] Example 2. Fabrication and assembly of application tool Prototypes and test models were designed using CAD software (Fusion 360, Autodesk) and 3D printed using a fused deposition modeling-based 3D printer (Pro2 Plus, Raise3D) and a stereolithography-based 3D printer (Form3B+, Formlabs). Most pieces were made from polylactic acid (PLA), a recyclable 3D printing material, and / or hard resin.

[0086] To develop a general concept for the prototype, a low-resolution (high layer height, e.g., 0.25 mm) FDM (fused deposition modeling) printer was used for initial fabrication. Selected prototype candidates were then printed at higher resolution (low layer height, e.g., 0.05 mm) using an FDM or SLA (stereolithography) printer. Once the piece was printed, a prefabricated microneedle patch was attached to the microneedle support. Then, either (i) the microneedle patch carrier and the surrounding area were connected with an adhesive material (e.g., tape), or (ii) a microneedle support with rigid sides was placed on top of the surrounding area. In the former embodiment, a rigid portion was placed on top of the adhesive material to prevent loosening, thereby reducing the force and speed of impact of the microneedle patch during insertion.

[0087] Example 3. Insertion of microneedle patches into artificial skin models and pig cadaver skin The fabricated microneedle patch was fixed to the carrier portion of the application tool using double-sided tape or adhesive spray. The microneedle patch carrier was then assembled with the remaining portion of the application tool. This was followed by alignment with an artificial skin model or pig cadaver skin. The final step was to apply sufficient force to break the release mechanism and rapidly move the microneedle into the skin model, resulting in insertion.

[0088] Figure 14 shows a representative bright-field image of the patch after application to an artificial skin model. The skin model contains eight layers of translucent flexible film (Parafilm™). The image shows that the microneedles successfully perforated the Parafilm layer of the skin model.

[0089] Example 4. Evaluation of insertion success and insertion depth The depth of insertion was assessed using an optical microscope by peeling back layers of the artificial skin model and examining the individual layers and the overall image of the porcine cadaver skin after insertion. An optical coherence tomography device was used to confirm the depth of insertion while the microneedles were inside the artificial skin model.

[0090] Figure 15 (A) shows an optical coherence tomography (OCT) image showing the insertion of a microneedle into an artificial skin model. The top and middle lines indicate the artificial skin model. The numbers on the right indicate the number of layers. A schematic representation of the imaging method is shown on the right (B).

[0091] Embodiment Some embodiments of the present disclosure can be described in consideration of one or more of the following.

[0092] Embodiment 1. A device for applying microneedles to skin or other biological tissue, the device comprising: (i) a support structure from which an array of microneedles extends; and (ii) an applicator portion including a release mechanism, and a base portion configured to abut the skin or other biological tissue and hold the applicator portion in a pre-fired position in which the microneedles face the skin or other biological tissue at a distance from the surface of the skin or other biological tissue, the applicator portion configured to receive a manually applied force such that when the force exceeds a predetermined threshold, the release mechanism triggers and releases the microneedles, together with at least a portion of the support structure, from the pre-fired position, thereby driving the microneedles along a guide path toward the skin or other biological tissue with a force and velocity effective to insert the microneedles into the skin or other biological tissue.

[0093] Embodiment 2. The device of embodiment 1, wherein the base portion includes a stabilizing portion configured to be positioned against the patient's skin so that the guide path is perpendicular to the surface of the skin at the target site of microneedle insertion.

[0094] Embodiment 3. A device as described in embodiment 2 or 3, wherein the base portion includes one or more outer walls defining an opening through which the microneedle is configured to move along the guide path together with at least a portion of the support structure.

[0095] Embodiment 4. A device described in any one of embodiments 1 to 3, wherein the one or more outer walls are provided with one or more guide rails or slots that matingly engage with one or more slots or guide rails of the applicator portion, respectively.

[0096] Embodiment 5. A device described in any one of embodiments 1 to 4, wherein the opening defined by the one or more walls of the base portion is cylindrical, and the applicator portion includes an elongated cylindrical body configured to translate within the opening.

[0097] Embodiment 6. A device according to any one of embodiments 1 to 5, wherein the release mechanism is configured to be triggered by mechanical disruption of a portion of the support structure.

[0098] Embodiment 7. A device according to any one of embodiments 1 to 6, wherein the support structure comprises a polymer film.

[0099] Embodiment 8. A device according to any one of embodiments 1 to 7, wherein the release mechanism comprises a plurality of perforations or predetermined lines of weakness in the support structure.

[0100] Embodiment 9. A device described in any one of embodiments 1 to 5, wherein the release mechanism is configured to be triggered by deformation of the latch arrangement.

[0101] Embodiment 10. The device of embodiment 9, wherein the latching arrangement comprises a lip on the applicator portion that interferes with a ledge on the wall of the base portion in the pre-fired position.

[0102] Embodiment 11. A device according to any one of embodiments 1 to 10, wherein the release mechanism is integral with the support structure.

[0103] Embodiment 12. A device according to any one of embodiments 1 to 10, wherein the release mechanism is separate from the support structure.

[0104] Embodiment 13. A device as described in embodiment 12, wherein the applicator portion comprises an elongated body having an upper end portion configured to receive a manually applied force and a lower end portion including an array of microneedles, and wherein the release mechanism is disposed between the upper end portion and the lower end portion.

[0105] Embodiment 14. A device according to any one of embodiments 1 to 13, configured to generate a velocity effective to insert the microneedle, between 1 m / s and 15 m / s, preferably about 8 m / s.

[0106] Embodiment 15. A device described in any one of embodiments 1 to 14, wherein the predetermined threshold of manually applied force is between 10N and 70N, preferably about 40N.

[0107] Embodiment 16. A device according to any one of embodiments 1 to 15, wherein the device is configured to apply two or more arrays of microneedles.

[0108] Embodiment 17. A device according to any one of embodiments 1 to 15, wherein the device is configured to apply two or more arrays or microneedles simultaneously.

[0109] Embodiment 18. A device according to any one of embodiments 1 to 15, wherein the device is configured to apply two or more arrays or microneedles in series.

[0110] Embodiment 19. A system comprising an insertion tool including a housing and a backing releasably attached to the housing, and an array of microneedles containing a substance of interest, the microneedles being provided on a bottom surface of the backing, wherein a force applied by a user to the backing is effective to separate the backing from the housing and insert the array of microneedles into biological tissue at a predetermined speed.

[0111] Embodiment 20. The system of embodiment 19, wherein the predetermined speed is between about 1 m / s and 15 m / s, preferably about 8 m / s.

[0112] Embodiment 21. A system described in embodiment 19 or 20, wherein the force applied by the user is about 10N to about 70N, preferably about 40N.

[0113] Embodiment 22. A system described in any one of embodiments 19 to 21, wherein the backing includes a top portion to which a user-applied force is applied, a middle portion configured to releasably attach the backing to the housing, and a bottom portion, and the array of microneedles is provided on the bottom surface of the bottom portion of the backing.

[0114] Embodiment 23. The system of embodiment 22, wherein the intermediate portion comprises a tape or film configured to break upon application of a user-applied force, thereby triggering said separation and insertion.

[0115] Embodiment 24. The system of embodiment 22 or 23, wherein the intermediate portion includes a predetermined fracture area configured to break upon application of a user-applied force to the backing, thereby triggering said separation and insertion.

[0116] Embodiment 25. A system described in any one of embodiments 19 to 21, wherein the backing comprises a top portion to which a user-applied force is applied, and a bottom portion, the bottom portion comprising a predetermined breaking area configured to break upon application of a user-applied force to the backing, thereby triggering said separation and insertion.

[0117] Embodiment 26. A system described in any one of embodiments 19 to 21, wherein the backing includes a predetermined fracture area configured to break upon application of a user-applied force to the backing, thereby triggering said separation and insertion.

[0118] Embodiment 27. A system described in any one of embodiments 19 to 21, wherein the backing is releasably attached to the housing via a predetermined fracture area configured to break upon application of a user-applied force to the backing, thereby triggering said separation and insertion.

[0119] Embodiment 28. A system described in any one of embodiments 19 to 27, further comprising a tissue support portion configured to support biological tissue from the side of the tissue opposite the force applied by the user.

[0120] Embodiment 29. The system of embodiment 28, wherein the tissue support portion is connected to the housing and defines a gap therebetween for receiving biological tissue.

[0121] Embodiment 30. A system described in any one of embodiments 19 to 27, wherein the backing is releasably attached to the housing via a latch mechanism, and a force applied by the user causes mechanical deformation to separate the backing from the housing and insert the array of microneedles.

[0122] Embodiment 31. A method comprising: positioning a base of an applicator tool against a surface of a target tissue, wherein an array of microneedles extends from the applicator disposed in a pre-fired position within the base, the microneedles facing the surface of the target tissue at a distance of at least 5 mm; manually applying a force above a predetermined threshold to an upper surface of the applicator tool, causing an ejection mechanism connecting the applicator to the base to trigger and eject the microneedles, along with at least a portion of the applicator, thereby causing the manually applied force to drive the microneedles along a guide path toward the surface of the tissue with a force and velocity effective to insert the microneedles into the skin or other biological tissue, wherein triggering the ejection mechanism comprises (i) mechanical disruption of a structure securing the applicator in a pre-fired position, or (ii) deformation of a latching arrangement.

[0123] Embodiment 32. The method of embodiment 31, wherein the velocity is about 1 m / s to about 15 m / s, preferably about 8 m / s.

[0124] Embodiment 33. The method of embodiment 31 or 32, wherein the separation distance is 5 mm to 3 cm, preferably about 15 mm.

[0125] Embodiment 34. The method of any one of claims 31 to 33, wherein the release mechanism connecting the applicator to the base comprises tape.

[0126] Embodiment 35. The method of any one of embodiments 31 to 34, wherein the release mechanism connecting the applicator to the base includes the applicator being held in contact with the base without being adhesively or integrally connected by forces associated with the arrangement and dimensions of the applicator and base.

[0127] Embodiment 36. A device for applying microneedles to skin or other biological tissue, the device comprising: an applicator including an array of microneedles; and a trigger mechanism operably connected to the applicator, the device configured to apply the array of microneedles to the skin at a controlled rate, force, and angle, the device having no stored energy, and the trigger mechanism not moving the array of microneedles toward the skin until a threshold manual force is applied to the device.

[0128] Embodiment 37. The device described in embodiment 36, further comprising a base connected to the applicator and the trigger mechanism, the base being configured to be placed against the surface of the skin and to stabilize the position of the applicator relative to the skin until a threshold manual force is applied to the device.

[0129] Embodiment 38. A device according to embodiment 36 or 37, wherein the microneedles are spaced a distance from the skin.

[0130] Embodiment 39. A device described in any one of embodiments 36 to 38, wherein the distance is about 5 mm to about 3 cm, preferably about 15 mm.

[0131] Modifications and variations of the methods and devices described herein will be obvious to those skilled in the art from the foregoing detailed description, and such modifications and variations are intended to fall within the scope of the appended claims.

Claims

1. 1. A device for applying microneedles to skin or other biological tissue, said device comprising: (i) a support structure from which the array of microneedles extends, and (ii) an applicator portion including a release mechanism; and a base portion configured to abut the skin or other biological tissue and hold the applicator portion in a pre-fired position with the microneedles facing the skin or other biological tissue at a distance from the surface of the skin or other biological tissue; Equipped with The applicator portion is configured to receive a manually applied force, and when the force exceeds a predetermined threshold, the release mechanism triggers and releases the microneedle, together with at least a portion of the support structure, from the pre-fired position, thereby driving the microneedle along a guide path toward the skin or other biological tissue with a force and velocity effective to insert the microneedle into the skin or other biological tissue.

2. 10. The device of claim 1, wherein the base portion includes a stabilizing portion configured to be positioned against the patient's skin so that the guide path is perpendicular to the surface of the skin at a target site of insertion of the microneedle.

3. The device of claim 1 , wherein the base portion includes one or more outer walls defining an opening through which the microneedle is configured to move along the guide path together with at least a portion of the support structure.

4. The device of claim 3 , wherein the one or more outer walls include one or more guide rails or slots that matingly engage with one or more slots or guide rails, respectively, of the applicator portion.

5. 4. The device of claim 3, wherein the opening defined by the one or more walls of the base portion is cylindrical, and the applicator portion includes an elongated cylindrical body configured to translate within the opening.

6. The device of claim 1 , wherein the release mechanism is configured to be triggered by mechanical disruption of a portion of the support structure.

7. The device of claim 6 , wherein the support structure comprises a polymer film.

8. The device of claim 6 , wherein the release mechanism comprises a plurality of perforations or predetermined lines of weakness in the support structure.

9. The device of claim 1 , wherein the release mechanism is configured to be triggered by deformation of a latching arrangement.

10. The device of claim 9 , wherein the latching formation comprises a lip on the applicator portion that interferes with a ledge on a wall of the base portion in the pre-fired position.

11. The device of claim 1 , wherein the release mechanism is integral with the support structure.

12. The device of claim 1 , wherein the release mechanism is separate from the support structure.

13. 13. The device of claim 12, wherein the applicator portion comprises an elongate body having an upper end portion configured to receive a manually applied force and a lower end portion including the array of microneedles, and the release mechanism is disposed between the upper end portion and the lower end portion.

14. 10. The device of claim 1, configured to generate a velocity effective to insert the microneedle of between 1 m / s and 15 m / s, preferably about 8 m / s.

15. The device of claim 1, wherein the predetermined threshold of manually applied force is between 10N and 70N, preferably about 40N.

16. The device of claim 1 , wherein the device is configured to apply two or more arrays of microneedles.

17. 17. The device of claim 16, wherein the device is configured to simultaneously apply two or more arrays or microneedles.

18. 17. The device of claim 16, wherein the device is configured to apply two or more arrays or microneedles in series.

19. 1. A system comprising:

1. An insertion tool comprising: Housing and a backing releasably attached to said housing; Insertion tools, including an array of microneedles containing a substance of interest, the array of microneedles being disposed on a bottom surface of the backing; Includes A system wherein a force applied by a user to the backing is effective to separate the backing from the housing and insert the array of microneedles into biological tissue at a predetermined speed.

20. 20. The system of claim 19, wherein the predetermined speed is between about 1 m / s and 15 m / s, preferably about 8 m / s.

21. 20. The system of claim 19, wherein the user-applied force is between about 10N and about 70N, preferably about 40N.

22. The backing is a top portion to which the user-applied force is applied; a middle portion configured to releasably attach the backing to the housing; and 20. The system of claim 19, comprising a bottom portion, the array of microneedles being disposed on a bottom surface of the bottom portion of the backing.

23. 23. The system of claim 22, wherein the intermediate portion comprises a tape or film configured to break upon application of a user-applied force, thereby triggering the separation and insertion.

24. 23. The system of claim 22, wherein the intermediate portion includes a predetermined fracture area configured to break upon application of a user-applied force to the backing, thereby triggering the separation and insertion.

25. The backing is a top portion to which the user-applied force is applied; and a base comprising a predetermined breakable area configured to break upon application of a force applied by the user to the backing, thereby triggering the separation and insertion; 20. The system of claim 19, comprising:

26. 20. The system of claim 19, wherein the backing includes a predetermined fracture area configured to break upon application of a user-applied force to the backing, thereby triggering the separation and insertion.

27. 20. The system of claim 19, wherein the backing is releasably attached to the housing via a predetermined breakable area configured to break upon application of a user-applied force to the backing, thereby triggering the separation and insertion.

28. 20. The system of claim 19, further comprising a tissue support portion configured to support the living tissue from a side of the tissue opposite the user-applied force.

29. 30. The system of claim 28, wherein the tissue support portion is connected to the housing and defines a gap therebetween for receiving the living tissue.

30. The system of claim 19, wherein the backing is releasably attached to the housing via a latching mechanism, and wherein a force applied by the user causes mechanical deformation to separate the backing from the housing and insert the array of microneedles.

31. 1. A method comprising: positioning a base of an applicator tool against a surface of a target tissue, with an array of microneedles extending from the applicator positioned within the base in a pre-fired position, the microneedles facing the surface of the target tissue at a distance of at least 5 mm apart; manually applying a force above a predetermined threshold to an upper surface of the applicator tool, causing a release mechanism connecting the applicator to the base to trigger and release the microneedle along with at least a portion of the applicator, thereby causing the manually applied force to drive the microneedle along a guide path toward a surface of the tissue with a force and velocity effective to insert the microneedle into the skin or other biological tissue; Including, The method, wherein the triggering of the release mechanism comprises (i) mechanical disruption of a structure that secures the applicator in the pre-fired position, or (ii) deformation of a latching arrangement.

32. 32. The method of claim 31, wherein the velocity is between about 1 m / s and about 15 m / s, preferably about 8 m / s.

33. A method according to claim 31 or 32, wherein the separation distance is between 5 mm and 3 cm, preferably about 15 mm.

34. 34. The method of any one of claims 31 to 33, wherein the release mechanism connecting the applicator to the base comprises tape.

35. 34. The method of any one of claims 31 to 33, wherein the release mechanism connecting the applicator to the base includes the applicator being held in contact with the base without being adhesively or integrally connected by forces associated with the arrangement and dimensions of the applicator and the base.

36. 1. A device for applying microneedles to skin or other biological tissue, said device comprising: an applicator comprising an array of microneedles; and a trigger mechanism operably connected to the applicator; Equipped with the device is configured to apply the array of microneedles to the skin at a controlled rate, force, and angle; A device wherein the device has no stored energy and the trigger mechanism does not move the array of microneedles toward the skin until a threshold manual force is applied to the device.

37. 37. The device of claim 36, further comprising a base connected to the applicator and trigger mechanism, the base configured to be placed against a surface of the skin and stabilize the position of the applicator relative to the skin until the threshold manual force is applied to the device.

38. 37. The device of claim 36, wherein in said position, said microneedles are spaced a distance from said skin.

39. 37. The device of claim 36, wherein the distance is between about 5 mm and about 3 cm, preferably about 15 mm.

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