Microneedle application tool and method

Abstract

A device or tool for applying microneedles to skin or other biological tissue is provided, where the device comprises: an applicator having an array of microneedles; and a trigger mechanism operably connected to the applicator. The device is configured to apply an array of microneedles to the skin at a controlled speed, force, and angle. The device does not store energy and the trigger mechanism does not allow the microneedle array to move toward the skin until a threshold manual force is applied to the device.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 406,023, filed on September 13, 2022, which is incorporated herein by reference.

[0003] Federally funded research and development

[0004] This invention was made with government support under Prime Contract No. 7200AA20CA00016 awarded by the United States Agency for International Development. The United States Government has certain rights in this invention. Background Art

[0005] Microneedle array devices are applied to biological tissues such as skin for various purposes, including but not limited to drug delivery (e.g., vaccination, contraceptive administration) and diagnosis. The microneedles of the array should generally be applied to the tissue with a certain force, speed, and insertion angle in order to achieve the desired penetration of the microneedles into the tissue. Insufficient insertion force, insufficient speed, or non-perpendicular insertion angle may unexpectedly result in incomplete or non-insertion and / or accidental breakage of the microneedle tip.

[0006] For example, conventional microneedle insertion may require user training to apply the correct force, speed and insertion angle so that the microneedle patch is successfully applied to the patient's skin. Alternatively or additionally, complex and / or expensive applicators or application systems may be required. For example, some conventional systems rely on energy stored in the microneedle patch or additional components associated with the patch to provide the microneedle insertion force. For example, energy can be stored in the form of a spring or elastic material, or it can be in the form of a battery that provides energy for the mobile components that apply the patch to the tissue. However, pre-stored energy may increase the risk of premature deployment of the microneedle array, which may result in waste of material and / or incorrect application. In addition, conventional tools with pre-stored energy may also require complex and specialized components, making them difficult and / or expensive to manufacture.

[0007] Self-administration of microneedle patches will improve user compliance and have a positive impact on many drug applications. However, given the importance of correctly applying microneedles to the skin or other tissues for proper insertion of the microneedles described above, user error must be minimized for self-administration. Therefore, it is desirable to provide new and improved tools that facilitate repeatable and effective insertion, which can increase the success rate of microneedle application. Ideally, such tools would be relatively simple and inexpensive to manufacture and easy to self-administer. Summary of the invention

[0008] In one aspect, a device or tool for applying microneedles to skin or other biological tissue is provided, wherein the device comprises: an applicator comprising a microneedle array; and a trigger mechanism operably connected to the applicator, wherein the device is configured to apply the microneedle array to the skin at a controlled speed, force, and angle, and wherein the device has no stored energy and the trigger mechanism does not allow the microneedle array to move toward the skin until a threshold manual force is applied to the device.

[0009] In certain embodiments, the device includes an applicator portion including (i) a support structure from which an array of microneedles extends and (ii) a release mechanism; and a base portion configured to rest against skin or other biological tissue and to hold the applicator portion in a pre-fire position in which the microneedles face the skin or other biological tissue and are spaced a spacing distance from the surface of the skin or other biological tissue, wherein the applicator portion is configured to receive a manually applied force that, when exceeding a predetermined threshold, causes the release mechanism to trigger and release the microneedles and at least a portion of the support structure from the pre-fire position, thereby driving the microneedles along a guide path toward the skin or other biological tissue at a force and speed effective to insert the microneedles into the skin or other biological tissue. The release mechanism can be configured to be triggered by mechanical rupture of a portion of the support structure (e.g., at a plurality of perforations or a predefined weakening line in the support structure), or by deformation of a latch feature.

[0010] In another aspect, a method is provided, the method comprising: positioning a base of an applicator tool against a target tissue surface, wherein a microneedle array extends from the applicator in a pre-fire position disposed within the base, wherein the microneedles face the target tissue surface and are separated from the target tissue surface by a spacing distance of at least 5 mm; manually applying a force exceeding 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 and at least a portion of the applicator, thereby driving the microneedles along a guide path toward the tissue surface via the manually applied force at a force and speed effective to insert the microneedles into skin or other biological tissue, wherein triggering of the release mechanism includes (i) mechanical rupture of a structure securing the applicator in the pre-fire position, or (ii) deformation of a latch feature. The speed may be between about 1 m / s and about 15 m / s, preferably about 8 m / s, and the spacing distance may be between 5 mm and 3 cm, preferably about 15 mm. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The detailed description is set forth with reference to the accompanying drawings. The use of the same reference numerals may represent similar or identical items. Various embodiments may utilize elements and / or components different from those shown in the accompanying drawings, and some elements and / or components may not be present in various embodiments. Elements and / or components are not necessarily drawn to scale.

[0012] Figure 1 is a perspective view of a microneedle patch according to one embodiment of the present disclosure.

[0013] Figure 2A is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0014] Figure 2B According to one or more embodiments of the present disclosure Figure 2A A perspective view of the base portion of a microneedle applicator tool.

[0015] Figure 2C According to one or more embodiments of the present disclosure Figure 2A An exploded perspective view of the applicator portion of a microneedle applicator tool.

[0016] Figure 3A is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0017] Figure 3B According to one or more embodiments of the present disclosure Figure 3A A perspective view of the base portion of a microneedle applicator tool.

[0018] Figure 3C According to one or more embodiments of the present disclosure Figure 3A An exploded perspective view of the application portion of a microneedle applicator tool.

[0019] Figure 4A is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0020] Figure 4B According to one or more embodiments of the present disclosure Figure 4A A perspective view of the base portion of a microneedle applicator tool.

[0021] Figure 4C According to one or more embodiments of the present disclosure Figure 4A A perspective view of the application portion of a microneedle applicator tool.

[0022] Figure 5 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0023] Figure 6 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0024] Figure 7 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0025] Figure 8 is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0026] Fig.9A is a perspective view of a microneedle applicator tool for simultaneously applying multiple microneedle patches according to one or more embodiments of the present disclosure.

[0027] Fig. 9B is a bottom plan view of a microneedle applicator tool for simultaneously applying multiple microneedle patches according to one or more embodiments of the present disclosure.

[0028] Fig. 9C is a bottom perspective view of a microneedle applicator tool for simultaneously applying multiple microneedle patches according to one or more embodiments of the present disclosure.

[0029] Fig.9D is a bottom plan view of a microneedle applicator tool for simultaneously applying multiple microneedle patches according to one or more embodiments of the present disclosure.

[0030] Fig.10 is a perspective view of a microneedle applicator tool for sequentially applying multiple microneedle patches according to one or more embodiments of the present disclosure.

[0031] Fig.11 is a partially transparent perspective view of a microneedle applicator tool for shear application according to one or more embodiments of the present disclosure.

[0032] Fig. 12A is a perspective view of a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0033] Fig. 12B According to one or more embodiments of the present disclosure Fig. 12A Side view of a microneedle applicator tool.

[0034] Fig.13 Depicted is the insertion of a microneedle patch using a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0035] Fig.14 is a representative bright field image showing the insertion of microneedles into an artificial skin model using a microneedle applicator tool according to one or more embodiments of the present disclosure.

[0036] Fig.15 is an optical coherence tomography (OCT) image showing the insertion of microneedles into an artificial skin model using a microneedle applicator tool according to one or more embodiments of the present disclosure. DETAILED DESCRIPTION

[0037] Microneedle application devices, systems and methods have been developed for applying microneedles to skin or other tissues more easily and effectively for medical or other purposes. Factors such as force, speed, acceleration and the angle between the patch surface and the tissue will affect the interaction between the patch and the tissue, and importantly, whether the microneedle pierces the tissue and the depth of the microneedle insertion into the tissue. The currently disclosed applicator device is configured to enable the user to apply sufficient and evenly distributed insertion force to the microneedle array, and to predictably obtain the desired insertion speed and insertion angle (e.g., perpendicular to the skin surface). Generally, the microneedle applicator tool disclosed herein stores energy when the user actively applies force to the tool, and releases the energy in a manner that effectively applies the microneedle to the skin when the energy threshold is accumulated and exceeded. If at any time the user stops applying force, any stored energy will be released, and no additional energy will be stored unless the user applies force to the tool again. That is, when no force is applied to the tool, the tool cannot store energy in the device.

[0038] Unlike conventional microneedle applicators and patch designs, the energy for applying the microneedle application tool described herein is provided only by the force manually applied to the application tool by the user (e.g., the user's thumb). Using the tool described herein, applying the insertion force to the microneedle does not involve energy from a battery or a separate spring element. The design of the device can be advantageously easier and more economical to manufacture and use, and can advantageously improve the reliability or effectiveness of self-administration. Advantageously, the microneedle application tool disclosed herein provides a high-impact application with a high speed while also ensuring a controlled (e.g., vertical) insertion angle.

[0039] The successful application of microneedles to the skin or other tissues generally depends on several parameters. First, the sharpness of the microneedle tips is critical. The currently disclosed applicators can advantageously shield and protect the microneedles until the moment of insertion. Second, the microneedles should generally be inserted vertically (although in some cases, non-vertical insertion may be ideal), and a sufficient amount of pressure should be evenly distributed across the microneedle patch. An angled insertion may break the microneedles or produce uneven or insufficient pressure, which may hinder insertion and drug delivery. The currently disclosed applicators advantageously facilitate uniform insertion of microneedles at a controlled (e.g., vertical) angle.

[0040] An important part of the kit disclosed herein is to have space between the microneedles and the skin (before the applicator is fired) to be able to obtain a high enough speed to insert the microneedles, such as a separation distance of at least 5 mm.

[0041] Applicator device (tool)

[0042] In some embodiments, a device for applying microneedles to skin or other biological tissue is provided, wherein the device includes: (a) an applicator portion, which includes (i) a support structure from which a microneedle array extends and (ii) a release mechanism; and (b) a base portion, which is configured to abut against the skin or other biological tissue and hold the applicator portion in a pre-fire position, in which the microneedles face the skin or other biological tissue and are separated from the surface of the skin or other biological tissue by a spacing distance, wherein the applicator portion is configured to receive a manually applied force that, when exceeding a predetermined threshold, causes the release mechanism to trigger and release the microneedles and at least a portion of the support structure from the pre-fire position, thereby driving the microneedles along a guide path toward the skin or other biological tissue with a force and speed effective to insert the microneedles into the skin or other biological tissue.

[0043] In some preferred embodiments, the device is configured to produce an effective microneedle insertion speed of 1 m / s to 15 m / s, preferably about 8 m / s. The lower speed can allow the target tissue to elastically deform when in contact with the microneedle, rather than being penetrated by the microneedle. The desired speed can be achieved by design factors including the spacing between the microneedle tip in the pre-fire position and the skin surface, and the force applied to the microneedle when fired. For example, in some preferred embodiments, the predetermined threshold of the manually applied force is 10N to 70N, preferably about 40N.

[0044] Factors such as microneedle geometry, number of microneedles, and / or density of microneedles in an array may affect the optimal insertion force. The release mechanism described herein can be modified to adjust the insertion force. For example, the insertion force can be adjusted by changing the construction material, thickness, and / or geometry of the release portion that is designed to fail due to fracture or elastic or plastic deformation. For example, using a thinner or perforated material for the release portion can reduce the insertion force, while a thicker material for the release portion can increase the insertion force.

[0045] The triggering of the release mechanism releases the energy temporarily stored in the applicator device, which is transmitted by the force applied by the user. The released energy can effectively launch the applicator portion and insert the microneedle array into the skin (or other biological tissue) without any additional energy source. That is, energy is stored only when the user applies force to the applicator device.

[0046] The base portion may include a stabilizing portion configured to be placed 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, and the microneedle and at least a portion of the support structure are configured to travel along the guide path in the opening. In some embodiments, the walls of the base portion include guide rails, and the applicator portion can translate along these guide rails. For example, the applicator portion may include a slot that cooperates with the guide rails. In some other embodiments, the applicator portion has a guide rail and the base portion has a matching slot. In some embodiments, the opening defined by 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.

[0047] In some embodiments, the release mechanism is integral to the support structure.

[0048] The release mechanism may be configured to be triggered by mechanical failure. In some embodiments, the release mechanism is configured to be triggered by mechanical rupture of a portion of the support structure. The support structure may include a polymer film, may include a plurality of perforations or predefined weakening lines, or a combination thereof.

[0049] In some embodiments, the release mechanism includes a tape or other thin film structure that is designed to break and release the energy stored therein when the force applied by the user exceeds the material's fracture strength (the ability to resist crack-based failure under an applied load). For example, the applied force may deform the structure beyond its elastic limit, causing it to break and release the energy stored therein. In some embodiments, the structure includes weakened areas to more precisely control the insertion force and speed of the microneedle patch. Weakened areas can be formed by reducing the thickness of the structure in specific areas and / or by including perforations or other defects to ensure that the structure fails at the desired area for uniform release.

[0050] The release mechanism can be configured to be triggered by elastic or plastic deformation beyond a specific point, which results in instantaneous displacement of the structural component that holds the applicator portion in the pre-fire position without breaking and releasing the energy stored therein. In some embodiments, the release mechanism is configured to be triggered by elastic deformation of a latch feature. For example, the latch feature can include a lip (e.g., a ring, a tab, other protrusion, etc.) on the applicator portion that interferes with a flange (e.g., another ring, a tab, other protrusion, etc.) on the wall of the base portion in the pre-fire position.

[0051] In some embodiments, the release mechanism is separate from the support structure. For example, the applicator portion may include an elongated body having an upper end portion configured to receive a manually applied force and a lower end portion including the microneedle array, wherein the release mechanism is disposed between the upper end portion and the lower end portion.

[0052] Microneedle arrays and patches

[0053] Essentially any microneedle array or microneedle patch can be used with the presently disclosed applicator. In a particular embodiment, the microneedle comprises an agent of interest to be administered to the skin or other biological tissue. For example, as known in the art, the microneedle array of the present disclosure can be a patch comprising dissolvable microneedles for administration.

[0054] Figure 1 An example of a microneedle patch with a microneedle array is depicted. The microneedle patch 100 includes a backing layer 110 from which a 10×10 array of microneedles 120 extends. The terms “backing layer” and “base substrate” or “substrate” are used interchangeably herein. Each microneedle 120 has a proximal end 122 and a distal tip end 126, which is directly or indirectly attached to the backing layer 110 via one or more proximal portions 124, and the distal tip end is sharp and can effectively penetrate biological tissue. The microneedle 120 has a tapered sidewall 128 between the proximal end 122 and the distal end 126 of the microneedle 120.

[0055] A variety of drugs can be formulated for delivery to biological tissue using the microneedle patch. As used herein, the term "drug" refers to a preventive, therapeutic, or diagnostic agent useful in medical applications, as well as an agent 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 for infectious diseases, therapeutic vaccines for cancer, neurological disorders, allergies, and smoking cessation or other addictions.

[0056] In some embodiments, the structure and composition of the microneedle arrays that can be used in the presently disclosed applicators are described in U.S. Pat. No. 10,265,511, U.S. Pat. No. 10,828,478, U.S. Pat. No. 10,940,301, U.S. Pat. No. 11,730,937, U.S. Pat. Nos. 2022 / 0401715 and 2023 / 164306, which are incorporated herein by reference.

[0057] Certain applicator devices, systems and methods

[0058] Figures 2A to 13Embodiments of microneedle application tools and systems and methods of using the same are shown. Typically, the microneedle application tool includes a base portion and an applicator portion (including a microneedle array) that is operably connected to the base portion. The tool includes a release mechanism that is configured to fail when sufficient downward force is manually applied to the applicator portion, so that the failure only uses the manually applied force to launch the microneedles toward the patient's skin. The microneedles are launched so that the microneedles penetrate the patient's skin at a desired predetermined speed. As used herein, "failure" refers to the breaking or deformation of the release mechanism.

[0059] FIG. 2A to FIG. 2C A microneedle application tool 200 is illustrated that includes a base portion 202 and an applicator portion 204 that is releasably attached to the base portion. The applicator portion 204 includes an upper portion 206, a release portion 208, and a backing portion 210. Figure 2A The tool 200 is shown with the applicator portion in a pre-fired position, with the microneedles facing the tissue surface and spaced a distance from the tissue surface.

[0060] The base portion 202 is configured to stabilize and orient the microneedle application tool 200 on biological tissue (e.g., the skin of a patient) during application of the microneedle array. The shape and size of the legs 212 of the base portion 202, which are intended to be placed against a tissue surface (not shown), are set to provide the desired stability and orientation. The legs 212 have a substantially square shape, but can have any other suitable shape. The legs 212 have a bottom opening 214 through which the microneedles of the applicator portion 204 are guided so as to insert the microneedles into the tissue.

[0061] In some embodiments, at least a portion (i.e., one side) of the base portion 202 is open to accommodate anatomical variability among potential users of the device, thereby facilitating operation of the applicator tool. For example, keeping a portion of the tool open ensures that the user can easily orient and grip the tool as needed to apply the necessary pressure to the applicator portion. In some cases, for example, a thumb can be more easily inserted into the tool, while the user's other fingers can support the bottom of the base near the application area.

[0062] The base portion 202 has a wall 216 extending upward from the foot 212 of the base 202 to form a U-shape, thereby defining a side opening 218 through which a user can place a thumb. The side opening 218 allows the thumb (i.e., the widest finger that can generate the greatest force) to be located within the tool 200 and move freely until the microneedle array is applied to the skin. When the applicator 204 passes through the inner cavity 220 of the base, the side opening 218 can also allow the user to maintain downward pressure on the applicator 204 without generating a rebound force.

[0063] The base portion 202 has a top side 222 configured to hold at least a portion of the applicator portion 204 in a pre-fire position in which the microneedles face the tissue surface and are spaced a distance from the tissue surface. The top side 222 of the base portion 202 has flanges 224 on opposite sides of the base 202 that are configured to hold at least a portion of the applicator portion 204, for example, along opposite edge regions of a portion of the applicator portion. Figure 2A As shown, the flange 224 is configured to retain a portion of the release portion 208 of the applicator 204 .

[0064] The base portion 202 also includes slots 226 that are elongated in a direction perpendicular to the bottom surface of the legs. The slots 226 are positioned on the side of the wall 216 facing the cavity 220. Each wall 216 may have at least one slot 226. FIG. 2A to FIG. 2C In the illustrated embodiment, one wall has exactly three slots, and two walls have exactly two slots. The slots 226 are configured to accommodate a mating rail 228 extending from the side of the applicator portion 204. The rail 228 is configured to slide vertically in the slot 226 so that when the applicator portion is translated toward the tissue surface, the applicator portion 204 (and the microneedle array extending therefrom) remains perpendicular to the tissue surface. The slots and rails are sized to limit the tilt and / or swing of the applicator portion in the base during the insertion of the microneedle, making the insertion process more accurate and repeatable. Each slot 226 has a T-shaped channel, but other channel shapes are also possible; however, it is preferred to include a channel shape that interlocks with the rail 228 to allow the rail to move only along one axis relative to the base portion (and thus move the applicator portion). It should be understood that the slot and rail features can be interchanged so that the base portion has rails and the applicator portion has slots.

[0065] like Figure 2A As shown, the applicator portion 204 is sized and shaped generally to be disposed within and translated through the cavity 220 of the base portion. However, a portion of the release portion 208 of the applicator portion extends laterally beyond the cavity 220 and contacts the flange 224 of the base portion 202. This portion of the release portion 208 of the applicator portion can be adhered or otherwise attached to the flange 224 of the base portion 202, particularly if the release portion is a highly flexible material, such as a tape or polymer film.

[0066] Applicator portion 204 may include upper portion 206, release portion 208 and backing portion 210. Microneedle array 230 extends from bottom side 232 of backing portion 210. Microneedle array (e.g., microneedle patch) may be releasably attached to bottom side 232 of backing portion 210. Upper portion 206 includes user force application area 242 located near the center of top surface 234 of upper portion 206, which indicates that the user should apply manual force (e.g., using thumb) to initiate the area where microneedles are applied. The user should apply downward force to the center of upper portion 206 so that release portion 208 fails uniformly and microneedle array is uniformly emitted toward the skin surface. Although user force application area 242 is depicted as a circle, it should be understood that other suitable shapes may be used. In the illustrated embodiment, user force application area 242 includes anti-slip features, in which the anti-slip features include multiple knots 244. In some other embodiments, the user force application area includes a recessed area and / or includes ridges or textures to facilitate user grip. In some embodiments, the application area 242 can be slightly raised from the top surface 234 of the upper portion 206 to further guide the user, such as in the form of a button (e.g., about 5 mm high). Such anti-slip features can also help prevent the user's thumb from shifting during use, thereby preventing slipping or shaking that may cause application failure.

[0067] When the release portion 208 fails, the applicator portion 204 Figure 2A For example, the release portion 208 may include a perforation 236, such as Figure 2C 236, which depicts the area in which the release portion 208 is configured to fail. The perforations 236 can help ensure that the release portion 208 fails in a specific area. That is, the release portion 208 should fail along the perforations 236 so that during insertion, the middle portion 238 of the release portion 208 remains with the rest of the applicator 204, while the edge region 240 of the release portion 208 remains attached to the base 202. In other words, the fact that the edge region 240 extends beyond the sides of the top portion 206 and the backing portion 210 and is directly attached to the base 202 promotes the release portion to fail along the perforations 236.

[0068] Microneedle application tool 200 can be made of any suitable material. In certain embodiments, base 202 and upper portion 206 and backing portion 210 of applicator 204 are made of the same material. In certain embodiments, base 202, upper portion 206 and backing portion 210 are made of two or more different materials. For example, base 202, upper portion 206 and / or backing portion 210 can be made of plastic, metal, ceramic, glass or any combination thereof. In certain embodiments, base portion 202, upper portion 206 and / or backing portion 210 can be made of recyclable and / or biodegradable material (such as recyclable and / or biodegradable plastic).

[0069] In some embodiments, the applicator of the microneedle application tool is different from the reference FIG. 2A to FIG. 2C The applicator described herein. For example, in some embodiments, the release portion is not separated from the upper portion and / or the backing portion of the applicator. For example, the release mechanism can be incorporated into the upper portion or the backing portion of the applicator. In some embodiments, the applicator is a single part including the release mechanism. In some embodiments, the applicator can be formed together with the base of the microneedle application tool.

[0070] FIG. 3A to FIG. 3C A microneedle applicator tool 300 is shown having a base portion 302 and an applicator portion 304. The applicator portion 304 includes an upper portion 306 and a backing portion 308. Figure 3A The tool 300 is shown with the applicator portion in a pre-fired position, with the microneedles facing the tissue surface and spaced a distance from the tissue surface.

[0071] The base portion 302 is similar to the reference FIG. 2A to FIG. 2C The base portion 202 is described. For example, the legs 312 of the base portion 302 can be substantially square and define a bottom opening 314 through which the microneedles of the applicator portion 304 pass to penetrate the skin. The base portion 302 has three walls 316 extending upward from the legs 312 of the base portion 302 to form a U-shape, thereby defining a side opening 318 through which a user can pass his thumb to hold the applicator portion 304 while it passes through the inner cavity 320 defined by the walls 316.

[0072] The base portion 302 also includes a top side 322 having an opening configured to receive the applicator portion 304. The top side 322 includes flanges 324 on opposing walls 316 of the base portion 302 that are configured to receive opposing sides of the backing portion 308. In the illustrated embodiment, each flange 324 has an upwardly directed protrusion 323 that is configured to pass through an opening 337 in the backing portion 308 to secure the backing portion 308 to the base portion 302.

[0073] The base portion 302 includes slots 326 positioned on the side of the wall 316 facing the cavity 320. Each wall 316 can have at least one slot 326. FIG. 3A to FIG. 3C In the embodiment shown, each wall has exactly three slots. The slots 226 are configured to receive mating rails 328 extending laterally from the sides of the upper portion 306. The rails 328 are configured to slide vertically within the slots 326.

[0074] The applicator portion 304 includes an upper portion 306 and a backing portion 308 having a microneedle array (not shown) extending from a bottom side 332 thereof.

[0075] like Figure 3C As shown, the backing portion 308 includes a weakened attachment point 333 connecting the side rings 335 and the middle portion 338 of the backing portion 308. The backing portion 308 is configured to fail at the attachment point 333, where the middle portion 338 of the backing portion 308 that holds the microneedles during insertion remains with the applicator portion 304, while the side rings 335 remain attached to the flange 324 of the base portion 302. Although not shown, the upper surface 334 of the upper portion 306 can include a user force application area that includes the anti-slip features of the applicator tool 200 as described above.

[0076] FIG. 4A to FIG. 4C Another embodiment of a microneedle applicator tool 400 is illustrated having a base portion 402 and an applicator portion 404. The applicator tool 400 and Figures 2A to 3C The difference shown is that the applicator portion 404 is a single component rather than an assembly of an upper portion and a release portion / backing portion.

[0077] The base portion 402 is similar to the reference FIG. 2A to FIG. 2C The base portion 202 is depicted. The legs 412 of the base portion 402 are substantially square and define a bottom opening 414 through which the microneedle array 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 legs 412 to form a U-shape and define side openings 418 through which a user can pass their thumbs to apply pressure on the applicator 404 as the applicator 404 passes through the inner cavity 420 defined by the walls 416 of the base portion 402.

[0078] The base 402 also has a transverse slot 411 located below the top side 422 of the base portion 402. The applicator portion can be slid horizontally into the transverse slot 411 to position the applicator portion in its pre-fire position.

[0079] The base 402 also includes slots 426 that are elongated in a direction perpendicular to the bottom surface of the legs. The slots 626 are positioned on the sides of the walls 416 of the face cavity 420. The slots 426 are configured to accommodate a mating rail 428 extending from the sides of the applicator portion 404. The rails 428 are configured to slide vertically within the slots 426 so that the applicator portion 204 (and the microneedle array extending therefrom) remains perpendicular to the tissue surface as the applicator portion 404 translates toward the tissue surface.

[0080] A microneedle array (not shown) is attached to the bottom side 432 of the applicator portion 404. Figure 4C As shown, the applicator portion 404 has a main central body region 438 disposed between two edge regions 440, and includes several rows of perforations 436 located between the body portion 438 and the edge region 430. The body portion 438 is configured to be, for example, sufficiently rigid to evenly distribute the insertion force on the microneedle array, thereby promoting uniform insertion of the microneedles. When sufficient force is applied to the top surface 434 of the body portion 438, the perforations 436 promote mechanical failure at a desired location between the body portion 438 and the edge region 440. In some other embodiments, instead of or in addition to the perforations, the applicator portion may include other features, such as weakened portions / regions, to control the failure force and location that produces the desired insertion speed and force to drive the microneedle insertion.

[0081] Under sufficient load, applicator portion 404 is designed to fail along perforation 436 such that main portion 438 is launched toward the tissue surface having the microneedles to insert the microneedles while edge region 440 remains disposed within transverse slot 411 .

[0082] Figure 5 Still another embodiment of a microneedle applicator tool 500 is illustrated. In this tool, a base portion 502 and an applicator portion 504 are formed together as a single piece, wherein the applicator portion is in a pre-fired position. The base portion 502 is similar to the microneedle applicator tool 500 described above. FIG. 2A to FIG. 2CThe base portion 202 is depicted. The legs 512 are substantially square and define a bottom opening 520 through which microneedles 530 extending from a bottom surface 532 of the applicator portion 504 can pass in order to apply the microneedles to the skin. The base portion 502 has three walls 516 extending upward from the legs 512 and forming a U-shaped side opening 518 through which a user can pass his or her thumb to apply pressure on an upper surface 534 of the applicator portion 504 as the applicator portion 504 passes through the inner cavity 514 defined by the walls 516 of the base portion 502. The inner side of the walls 516 includes a plurality of slots 526 that open toward the cavity 514. The slots 526 are configured to accommodate mating rails 528 extending from the sides of the applicator portion 504. The guide rail 528 is configured to slide vertically within the slot 526 so that the applicator portion 504 (and the microneedle array extending therefrom) remains perpendicular to the tissue surface as the applicator portion 504 translates toward the tissue surface.

[0083] At the upper side 522 of the base portion, the applicator portion 504 and the base portion are connected to each other by two weakened areas 531, which include a row of perforations 536. When a sufficient load is applied downward on the upper surface 534, the applicator portion 504 and the base portion 502 separate (break) along the perforations 536, so that the applicator portion and the microneedle are launched toward the tissue surface for insertion of the microneedle.

[0084] The microneedle application tools described herein are generally configured for applying microneedles to relatively flat skin areas of a patient's limbs or other body parts, but these tools can be easily adapted to other biological tissues that may or may not be substantially flat. In some other embodiments, it is useful to apply the microneedle patch to a thin, flexible tissue that can be maintained in a relatively flat orientation to accommodate 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 treatments, vaccinations, identification, or tracking purposes.

[0085] Thus, the microneedle application tool described above may be adapted to further include an attached or detached tissue support structure configured to support and orient the flat tissue when applying the microneedle patch.

[0086] Figure 6 A microneedle application tool 600 is illustrated 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 those previously described with reference to FIG. Figures 2A to 5 Those structures and functions of the microneedle application tool described.

[0087] Base 602 is similar to FIG. 3A to FIG. 3CThe base portion 302 of the present invention is provided. The base 602 has a top side 608, which is configured to hold at least a portion of the applicator 604 thereon. The top side 608 of the base 602 includes flanges 610 located on opposite sides of the base 602, which are configured to hold the applicator 604. The flange 610 has a protrusion 611 protruding upward for further fixing the applicator 604 to the base 602. The base 302 may also include rails (not shown), which may be similar to the rails described with respect to any of the aforementioned embodiments. The base 602 also includes a hook 612 for attaching a strap 614 to the application tool 600. The strap 614 may be an elastic strap and may help to further stabilize the application tool 600 in the user's hand during use. For example, the user may place his thumb (or other fingers for pressing the applicator 604) between the strap 614 and the applicator 604, thereby helping to fix the application tool 600 to the user.

[0088] Applicator 604 is similar to FIG. 3A to FIG. 3C Applicator portion 304. Applicator 604 includes an upper portion 616 and a backing portion 618. A microneedle array (not shown) can be located on the bottom side of backing portion 618 so that when a user applies sufficient downward force to the top side 620 of top portion 616, applicator 604 is released from base portion 602 and the microneedles are applied to the skin.

[0089] In use, the base 602 and the applicator 604 are placed on one side of the target tissue (e.g., the skin on the ear of an animal), and the tissue support portion 606 is placed 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 to hold and control the support portion for the user. Therefore, the platform 622 is placed on the target tissue at a position relative to the base 602 to effectively support the base 602, thereby ensuring that the microneedle is correctly inserted. In the illustrated embodiment, the handle 624 has a ring shape so that the support portion can be worn on the user's finger, thereby facilitating the use of the application tool 600. The ring can be adjusted to accommodate different fingers and / or different users.

[0090] Figure 7 Another embodiment of a microneedle application tool 700 is shown, which has a base 702, an applicator 704, and a tissue support portion 706. The base 702 and the applicator 704 can be similar to Figure 5704. The base 702 and applicator 704 can be formed as a single piece, wherein the applicator 704 is attached near the top side 708 of the base 702 via one or more weakened areas that are configured to fail when a sufficient amount of force is applied to the applicator 704. The base 702 and the 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 that it contacts at least the platform 714, and in some embodiments, contacts 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 advances toward the tissue. Thus, the connecting portion 712 of the tool 700 is preferably flexible or otherwise adjustable so that it can be configured to vary the height of the gap within a useful range of tissue thicknesses so that the tissue can be securely in contact with the legs of the base while also being supported by the tissue support portion 706. The tissue support portion also includes a handle 716, which can be a reference Figure 6 Description of the ring.

[0091] Figure 8 Another embodiment of a microneedle application tool 800 is illustrated, the tool 800 having a base 802, an applicator 804, and a tissue support portion 806. The base 802 has an arched shape, and the applicator 802 has two legs 808, defining a bottom gap 810 between the two legs, through which the applicator 804 translates a microneedle array (not shown) toward and into the tissue. The applicator 804 is disposed 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) at which the applicator 804 is attached to the base 802. The weakened portion is configured to fail mechanically so that the microneedle array is applied to the tissue, similar to the other embodiments described above.

[0092] An upper opening 816 is defined between the applicator 804 and the arch 814, into which a user may place his or her thumb (or another finger) to apply an insertion force to the applicator 804. The base 802 includes hooks 818 located above the applicator 804, which may be used to secure a strap (not shown) to the base 802 to accommodate users with different anatomical features.

[0093] In use, the base 802 and the applicator 804 are placed on one side of the target tissue (e.g., the skin on the ear of an animal), 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 the user to hold and control the support portion. The platform 820 can be placed on the tissue in a position opposite to the base 802 to effectively support the base 802 thereon, thereby ensuring that the microneedles are properly inserted. In some embodiments, the top of the platform 820 is covered or coated with a material to prevent the tissue from sliding and / or provide additional comfort when applying the microneedles.

[0094] The microneedle applicator tool can be configured to utilize a single applicator to apply multiple microneedle patches. In certain embodiments, the microneedle applicator tool is configured to apply multiple microneedle patches simultaneously. In certain embodiments, the microneedle applicator tool is configured to continuously apply multiple microneedle patches in series. In some such embodiments, the applicator includes a top portion, a release portion and a backing portion. In some other such embodiments, the applicator includes a top portion and a backing portion. In other such embodiments, the applicator is a single part. In other such embodiments, the applicator and the base are formed as a single part.

[0095] 9A to 9C A microneedle application tool 900 configured to apply two microneedle patches simultaneously is illustrated. The microneedle application tool 900 includes a base 902 and an applicator 904. The base 902 and the applicator 904 may be similar to those of the reference Figures 2A to 5 A base portion and an applicator portion as described in any of C.

[0096] like Fig. 9B As shown, the bottom side 906 of the applicator 904 is divided into a plurality of different blocks 908a and 908b, to which microneedle arrays 914a and 914b are attached, respectively. The blocks 908a, 908b are separated by a gap 910, which is configured to accommodate a mating stop 912 of the base 902 when the applicator is fired / microneedles are inserted. Because the base 902 can have a larger profile to accommodate multiple microneedle patches, the stop 912 can also provide additional stability for the base 902.

[0097] The microneedle application tool 900 is configured to apply two different microneedle arrays. The applicator 904 has two blocks 908a and 908b and is configured to apply two microneedle arrays 914a and 914b simultaneously. The applicator tool can be adapted to apply other numbers of microneedle patches and arrays such as 3, 4, 5, 6, 7, 8, 9 or 10 (or more) microneedle arrays. For example, Fig. 9CAn applicator 950 is shown having four blocks 958 and configured to apply four microneedle arrays 954 simultaneously.

[0098] Fig.10 An embodiment of a microneedle application tool 1000 is illustrated, which is configured to apply a plurality of microneedle arrays in series. The microneedle application tool 1000 includes a base 1002 with a plurality of applicators 1004. The base 1002 and the applicators 1004 may be similar to those of the reference Figures 2A to 5 A base portion and an applicator portion as described in any one of C.

[0099] The base 1002 includes a plurality of openings 1006 for receiving the applicator 1004 therein. Adjacent openings may be separated by legs 1008 to maintain separation between the microneedle arrays.

[0100] Base 1002 can have any suitable number of openings depending on the number of microneedle arrays to be applied. For example, microneedle application tool 1000 can be configured to apply 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more microneedle arrays. Fig.10 In the illustrated embodiment, the microneedle application tool 1000 has four applicators 1004 .

[0101] In certain embodiments, the microneedle application tool can be configured to insert the microneedle array into the skin and apply a shear force, for example, to facilitate separation of the microneedles from the patch substrate.

[0102] Fig.11 A microneedle application tool 1100 for inserting a microneedle array using shear force is illustrated, wherein the application tool 1100 includes a base 1102 and an applicator 1104. The base 1102 and the applicator 1104 may be similar to those described with respect to Figures 2A to 5C. In some embodiments, the applicator includes a top portion, a release 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 part. In some embodiments, the applicator is formed as a single part with the base. The base 1102 is configured to support an applicator 1104 having a top portion 1106 and a bottom portion 1108 connected by an angled guide rail 1110. The base 1102 can also define a gap 1112 between the bottom portion 1108 and the skin, wherein the applicator 1104 can pass through the gap 1112 to apply the microneedles to the skin. The top 1106 of the applicator 1104 includes a predefined weakened portion, which is configured to fail when a sufficient amount of downward force is applied to the applicator 1104. When the weakened portion fails, the guide rail 1110 can enable the applicator to move along the y-axis, and then move along the x-axis to apply the microneedles to the skin (e.g., L-shaped motion). That is, the applicator 1104 will first advance vertically to insert the microneedles perpendicularly into the tissue and will then begin advancing horizontally to apply a shear force to the microneedles, thereby separating the microneedles from the backing.

[0103] like FIG. 12A to FIG. 12B As shown, a microneedle application tool 1200 for applying a microneedle array to biological tissue includes a base 1202 and an applicator 1204, wherein the base 1202 includes a guide portion 1206, a stabilizing portion 1208, and a microneedle support portion 1210 disposed therebetween. The base 1202 (more specifically the stabilizing portion 1208) is configured to stabilize and orient the microneedle application tool 1200 on biological tissue (e.g., the skin of a patient) during the application of the microneedle array. The legs 1212 of the stabilizing portion 1208 of the base 1202 can be substantially circular and define a bottom opening (not shown), through which the applicator 1204 can pass, so that the microneedles are applied to the skin. Although the legs 1212 of the base 1202 are shown as circular, it should be understood that other geometric shapes are also possible and are contemplated by the present disclosure. For example, the legs of the base can have any shape, such as a square or a rectangle.

[0104] The stabilizing portion 1208 can extend upward at an angle from the foot 1212 and have at least one protrusion 1214 extending upward from a top surface 1216 of the stabilizing portion 1208. The protrusion 1214 can be configured to receive and retain the microneedle supporting portion 1210 through a corresponding slot 1218 therein. The protrusion 1214 can also define a space therein that is configured to receive the guide portion 1206 of the base 1202 so that the guide portion 1206 can rest on top of the microneedle supporting portion 1210.

[0105] The guide portion 1206 is substantially cylindrical, with a bottom portion 1220 positioned above the stabilizing portion 1208 and the microneedle supporting portion 1210, a cylindrical middle portion 1222 extending upward from the bottom portion 1220, and a lateral arm 1224 positioned on top of the middle portion 1222. The lateral arm 1224 can help a user hold the applicator tool 1200 during use. The middle portion 1222 includes a window 1226 through which the applicator 1204 can be seen. The window 1226 can also advantageously allow air between the applicator 1204 and the guide portion 1206 to escape as the applicator 1204 travels within the guide portion 1206, thereby mitigating any negative effects that the compressed air may have on the application force and / or speed. In use, the applicator 1204 is configured to apply the microneedle array to the patient's skin. The applicator 1204 can include an elongated body 1228 slidably disposed within the guide portion 1206 and a stop 1230 configured to abut the lateral arm 1224 of the guide portion 1206 when the applicator 1204 has successfully applied the microneedle array to the skin.

[0106] The applicator 1204 includes a lip 1232 disposed about the circumference of the elongated body 1228. The lip 1232 is configured to rest on or within a corresponding flange 1234 of the guide portion 1206, the flange 1234 defining 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 flange 1234. As the force continues, the lip 1232 can deform the flange 1234 to the extent that the flange 1234 will release the lip 1232, thereby releasing the applicator 1204 to apply the microneedles to the skin. In some alternative embodiments, the lip rather than the flange can undergo a deformation that triggers the release. In various embodiments, the deformation of the lip and the flange can be elastic, plastic, or a combination thereof.

[0107] Application method

[0108] Fig.13 An exemplary method of using the microneedle tool and system disclosed herein is illustrated. Generally, the method includes placing an application tool having a base and an applicator portion on a target tissue, and applying an effective amount of downward force to the applicator portion to facilitate the release of the applicator from the base. When the applicator is released from the base, the applicator will move toward the target tissue to obtain a speed sufficient to apply the microneedles to the target tissue. Factors affecting speed include the amount of energy stored in the tool by the force applied by the user before triggering the release of the applicator, and the distance between the microneedle and the tissue surface before the applicator is released. In a specific embodiment, the applicator is designed to produce a selected velocity profile to provide maximum velocity during microneedle contact / insertion.

[0109] like Fig.13 As shown, the microneedle application tool 1300 has a base 1302 and an applicator 1304, wherein the applicator 1304 includes a top portion 1306, a release portion 1308, and a backing portion 1310 attached with a microneedle array 1312. As shown in step (a), the base 1302 of the microneedle application tool 1300 is placed on the target tissue surface 1314, so that the longitudinal axis of the microneedle 1312 is substantially perpendicular to the tissue surface 1314, wherein the tip end of the microneedle points to the tissue surface and is spaced apart from the tissue surface.

[0110] After the microneedle application tool 1300 is correctly placed on the target tissue surface 1314, the user manually applies force to the top portion 1306 of the applicator 1304 until the release portion 1308 fails and releases the applicator 1304 from its pre-launch position in the base. The release portion 1308 is configured to mechanically fail in response to sufficient user-applied force. For example, the release portion 1308 can be formed of a material that can be stretched or strained to a threshold point, at which the material will break (i.e., fail). In some embodiments, the force required for the release portion 1308 to fail is between about 10N and about 70N, such as between about 10N and 60N, between about 20N and about 50N, between about 30N and about 50N, or about 40N.

[0111] When the applicator 1304 is released from the base 1302, the applicator 1304 travels down to the tissue surface and vertically inserts the microneedle array 1312 into the tissue 1314. When the application tool 1300 is assembled prior to use, the distance that the applicator 1304 travels depends on the height of the base 1302 and the height of the microneedle array 1312 above the tissue 1314. In some embodiments, the height is about 5 mm to about 3 cm, such as about 10 mm to about 20 cm, about 5 mm to about 15 mm, or about 15 mm.

[0112] The speed at which the applicator 1304 moves toward the tissue 1314 can be proportional to the force applied to the applicator 1304 to cause the release portion 1308 to fail and / or the distance the applicator 1304 travels to apply the microneedle array 1312 to the tissue. For example, a higher failure force may cause the microneedles 1312 to be applied at a higher insertion speed. In some embodiments, the speed of the microneedle array 1312 is between about 1 m / s and about 15 m / s, such as 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.

[0113] Example

[0114] The present invention may be further understood with reference to the following non-limiting examples.

[0115] Example 1 Fabrication of microneedle patch

[0116] The microneedle array was fabricated using a solvent casting method. 90 μL of a water-based solution consisting of 18% PVA and 18% sucrose (w / w) was cast on the microneedle mold and dried at room temperature for 24 hours. After demolding, the microneedle (array) patch was stored in a desiccator for at least 24 hours for further drying.

[0117] Example 2 Fabrication and Assembly of Application Tools

[0118] Prototypes and test models were designed using CAD software (Fusion 360, Autodesk) and 3D printed using fused deposition modeling-based 3D printers (Pro2 Plus, Raise3D) and stereolithography-based 3D printers (Form3B+, Formlabs). Most of the parts were made of polylactic acid (PLA) (a recyclable 3D printing material) and / or rigid resin.

[0119] Initial manufacturing is performed using an FDM (fused deposition modeling) printer at a lower resolution (high layer height, such as 0.25mm) to obtain an overall concept of the prototype. Then, the selected candidate prototype is printed using an FDM or SLA (stereolithography) printer at a higher resolution (lower layer height, such as 0.05mm). Once these parts are printed, the previously manufactured microneedle patch is attached to the microneedle support. Then, (i) the microneedle patch carrier and the surrounding part are connected with an adhesive material (e.g., tape), or (ii) a microneedle support with a rigid side is placed on top of the surrounding part. In the previous embodiment, the rigid part is placed on top of the adhesive material to prevent loosening, otherwise this will reduce the impact force and speed of the microneedle patch when inserted.

[0120] Example 3 Insertion of microneedle patches into artificial skin models and cadaveric pig skin

[0121] The fabricated microneedle patch is fixed to the carrier part of the application tool with double-sided tape or spray adhesive. Next, the carrier with the microneedle patch is assembled with the rest of the application tool. This is followed by comparison on an artificial skin model or dead pig skin. The last step is to apply enough force to break the release mechanism, quickly move the microneedle to the skin model, and provide insertion.

[0122] Fig.14 Representative bright field images after applying the patch to an artificial skin model are shown. The skin model consists of eight layers of translucent flexible membranes (Parafilm TM). The image shows that the microneedles successfully penetrated the parafilm layer of the skin model.

[0123] Example 4 Evaluation of insertion success and insertion depth

[0124] The insertion depth was evaluated using an optical microscope by peeling off the layers of the artificial skin model and examining each layer and the overall image of the dead pig skin after insertion. When the microneedle was inside the artificial skin model, an optical coherence tomography device was used to examine the insertion depth.

[0125] Fig.15 is an optical coherence tomography (OCT) image (A) showing the insertion of microneedles in an artificial skin model. The top and middle lines show the artificial skin model. The numbers on the right indicate the number of layers. A schematic diagram of the imaging method is shown on the right (B).

[0126] Example

[0127] Some embodiments of the present disclosure may be described in terms of one or more of the following embodiments.

[0128] Embodiment 1 A device for applying microneedles to skin or other biological tissues, the device comprising: an applicator portion, the applicator portion comprising (i) a support structure from which a microneedle array extends and (ii) a release mechanism; and a base portion, the base portion being configured to abut against the skin or other biological tissue and to hold the applicator portion in a pre-fire position, in which the microneedles face the skin or other biological tissues and are separated from the surface of the skin or other biological tissues by a spacing distance, wherein the applicator portion is configured to receive a manually applied force that, when exceeding a predetermined threshold, causes the release mechanism to trigger and release the microneedles and at least a portion of the support structure from the pre-fire position, thereby driving the microneedles along a guide path toward the skin or other biological tissues with a force and speed effective to insert the microneedles into the skin or other biological tissues.

[0129] Example 2 A device according to Example 1, wherein the base portion includes a stabilizing portion, which is configured to be placed 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.

[0130] Embodiment 3 is a device according to embodiment 2 or 3, wherein the base portion includes one or more outer walls, the outer walls define an opening, and the microneedle and at least a portion of the support structure are configured to travel along the guide path in the opening.

[0131] Embodiment 4 is a device according to any one of embodiments 1 to 3, wherein the one or more outer walls include one or more guide rails or slots, and the one or more guide rails or slots are respectively engaged with one or more slots or guide rails of the applicator part.

[0132] Example 5 A device according to any one of Examples 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.

[0133] Example 6 The device according to any one of Examples 1 to 5, wherein the release mechanism is configured to be triggered by mechanical rupture of a portion of the support structure.

[0134] Embodiment 7 According to any one of embodiments 1 to 6, the device, wherein the support structure comprises a polymer film.

[0135] Embodiment 8 The device according to any one of embodiments 1 to 7, wherein the release mechanism comprises a plurality of perforations or predefined weakening lines in the support structure.

[0136] Example 9 The device of any one of Examples 1 to 5, wherein the release mechanism is configured to be triggered by deformation of the latch feature.

[0137] Example 10 The device of Example 9, wherein the latch feature includes a lip on the applicator portion, and in the pre-fire position, the lip interferes with a flange on the wall of the base portion.

[0138] Embodiment 11 is a device according to any one of embodiments 1 to 10, wherein the release mechanism is integrated with the support structure.

[0139] Embodiment 12 A device according to any one of embodiments 1 to 10, wherein the release mechanism is separated from the support structure.

[0140] Example 13 is a device according to Example 12, wherein the applicator portion includes an elongated body having an upper end portion configured to receive a manually applied force and a lower end portion including the microneedle array, wherein the release mechanism is disposed between the upper end portion and the lower end portion.

[0141] Embodiment 14 According to any one of embodiments 1 to 13, the device is configured to generate a speed effective for inserting the microneedle, the speed being 1 m / s to 15 m / s, preferably about 8 m / s.

[0142] Embodiment 15 is a device according to any one of embodiments 1 to 14, wherein the predetermined threshold value of the manually applied force is 10N to 70N, preferably about 40N.

[0143] Embodiment 16 According to any one of embodiments 1 to 15, the device is configured to apply more than one microneedle array.

[0144] Embodiment 17 According to any one of embodiments 1 to 15, the device is configured to apply more than one array or microneedle simultaneously.

[0145] Embodiment 18 A device according to any one of embodiments 1 to 15, wherein the device is configured to apply more than one array or microneedle in series.

[0146] Example 19 A system comprising: an insertion tool comprising: a shell; and a backing, the backing being releasably attached to the shell; and a microneedle array, the microneedle array comprising a substance of interest, wherein the microneedle array is disposed on the bottom side of the backing; wherein a user-applied force on the backing effectively separates the backing from the shell and inserts the microneedle array into biological tissue at a predetermined speed.

[0147] Embodiment 20 A system according to embodiment 19, wherein the predetermined speed is between about 1 m / s and 15 m / s, preferably about 8 m / s.

[0148] Example 21 A system according to Example 19 or 20, wherein the force applied by the user is between about 10N and about 70N, preferably about 40N.

[0149] Embodiment 22 is a system according to any one of embodiments 19 to 21, wherein the backing comprises: a top portion, on which the force applied by the user is applied; a middle portion, which is configured to releasably attach the backing to the shell; and a bottom portion, wherein the microneedle array is disposed on a bottom side of the bottom portion of the backing.

[0150] Example 23 A system according to Example 22, wherein the intermediate portion includes a tape or a film, and the tape or film is configured to fail when the user-applied force is applied, thereby triggering the separation and insertion.

[0151] Embodiment 24 A system according to Embodiment 22 or 23, wherein the middle portion includes a predefined breaking area, and the predefined breaking area is configured to fail when the force applied by the user is applied to the backing, thereby triggering the separation and insertion.

[0152] Example 25 A system according to any one of Examples 19 to 21, wherein the backing comprises: a top portion, on which the force applied by the user is applied; and a bottom portion, which comprises a predefined breaking area, and the predefined breaking area is configured to fail when the force applied by the user is applied to the backing, thereby triggering the separation and insertion.

[0153] Embodiment 26 A system according to any one of Embodiments 19 to 21, wherein the middle portion includes a predefined fracture area, and the predefined fracture area is configured to fail when the force applied by the user is applied to the backing, thereby triggering the separation and insertion.

[0154] Example 27 A system according to any one of Examples 19 to 21, wherein the backing is releasably attached to the shell via a predefined breaking area, and the predefined breaking area is configured to fail when the force applied by the user is applied to the backing, thereby triggering the separation and insertion.

[0155] Example 28 According to the system described in any one of Examples 19 to 27, the system further comprises a tissue support portion, wherein the tissue support portion is configured to support the biological tissue from a side of the tissue opposite to the force applied by the user.

[0156] Example 29 The system of Example 28, wherein the tissue support portion is connected to the shell and defines a gap therebetween to accommodate the biological tissue.

[0157] Embodiment 30 A system according to any one of embodiments 19 to 27, wherein the backing is releasably attached to the housing via a latch mechanism, and the force applied by the user causes mechanical deformation to separate the backing from the housing and insert the microneedle array.

[0158] Embodiment 31 A method, comprising: positioning a base of an applicator tool against a target tissue surface, wherein a microneedle array extends from an applicator disposed in a pre-fire position within the base, wherein the microneedles face the target tissue surface and are separated from the target tissue surface by a spacing distance of at least 5 mm; manually applying a force exceeding 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 and at least a portion of the applicator, thereby driving the microneedles along a guide path toward the tissue surface via the manually applied force at a force and speed effective to insert the microneedles into skin or other biological tissue, wherein triggering of the release mechanism includes (i) mechanical fracture of a structure that secures the applicator in the pre-fire position, or (ii) deformation of a latch feature.

[0159] Embodiment 32 is a method according to embodiment 31, wherein the speed is between about 1 m / s and about 15 m / s, preferably about 8 m / s.

[0160] Example 33 A method according to Example 31 or 32, wherein the spacing distance is 5 mm to 3 cm, preferably about 15 mm.

[0161] Embodiment 34 The method of any one of claims 31 to 33, wherein the release mechanism connecting the applicator to the base comprises tape.

[0162] Example 35 A method according to any one of Examples 31 to 34, wherein the release mechanism connecting the applicator to the base includes a force attached to the arrangement and size of the applicator and the base to keep the applicator in contact with the base without adhesion or integral connection.

[0163] Embodiment 36 A device for applying microneedles to skin or other biological tissue, the device comprising: an applicator comprising a microneedle array; and a trigger mechanism operably connected to the applicator, wherein the device is configured to apply the microneedle array to the skin at a controlled speed, force, and angle, and wherein the device has no stored energy and the trigger mechanism does not allow the microneedle array to move toward the skin until a threshold manual force is applied to the device.

[0164] Example 37 The device according to Example 36 further includes a base, which is connected to the applicator and the trigger mechanism and is configured to be placed against the skin surface and stabilize the position of the applicator relative to the skin until the threshold manual force is applied to the device.

[0165] Embodiment 38 A device according to Embodiment 36 or 37, wherein, at the position, the microneedles are separated from the skin by a certain distance.

[0166] Embodiment 39 is a device according to any one of Embodiments 36 to 38, wherein the distance is about 5 mm to about 3 cm, preferably about 15 mm.

[0167] Modifications and variations of the methods and apparatus described herein will be apparent to those skilled in the art from the foregoing detailed description. Such modifications and variations are intended to fall within the scope of the appended claims.

Claims

1. A device for applying microneedles to skin or other biological tissue, the device comprising: an applicator portion comprising (i) a support structure from which the microneedle array extends and (ii) a release mechanism; as well as a base portion configured to rest against the skin or other biological tissue and to hold the applicator portion in a pre-fire position in which the microneedles face the skin or other biological tissue and are spaced a spacing distance from the surface of the skin or other biological tissue, The applicator portion is configured to receive a manually applied force which, when exceeding a predetermined threshold, causes the release mechanism to trigger and release the microneedle and at least a portion of the support structure from the pre-fire position, thereby driving the microneedle along a guide path toward the skin or other biological tissue at a force and speed effective to insert the microneedle into the skin or other biological tissue.

2. The device according to claim 1, wherein: The base portion includes a stabilizing portion configured to be placed against the skin of a patient such that the guide path is perpendicular to the surface of the skin at a target site for insertion of the microneedles.

3. The device according to claim 1, wherein: The base portion includes one or more outer walls defining an opening, and the microneedle and at least a portion of the support structure are configured to travel along the guide path in the opening.

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

5. The device according to 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 according to claim 1, wherein: The release mechanism is configured to be triggered by a mechanical breakage of a portion of the support structure.

7. The device according to claim 6, wherein: The support structure includes a polymer film.

8. The device according to claim 6, wherein: The release mechanism comprises a plurality of perforations or predefined weakening lines in the support structure.

9. The device according to claim 1, wherein: The release mechanism is configured to be triggered by deformation of the latch feature.

10. The device according to claim 9, wherein: The latch feature includes a lip on the applicator portion that interferes with a flange on a wall of the base portion in the pre-fire position.

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

12. The device according to claim 1, wherein: The release mechanism is decoupled from the support structure.

13. The device according to claim 12, wherein: The applicator portion includes an elongated body having an upper end portion configured to receive a manually applied force and a lower end portion including the microneedle array, wherein the release mechanism is disposed between the upper end portion and the lower end portion.

14. The device of claim 1, configured to produce a velocity effective for inserting the microneedle, the velocity being between 1 m / s and 15 m / s, preferably about 8 m / s.

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

16. The device according to claim 1, wherein The device is configured to apply more than one microneedle array.

17. The device according to claim 16, wherein: The device is configured to apply more than one array or microneedle simultaneously.

18. The device according to claim 16, wherein: The device is configured to apply more than one array or microneedle in series.

19. A system, comprising: An insertion tool, the insertion tool comprising: a housing; and a backing releasably attached to the housing; and a microneedle array comprising a substance of interest, wherein the microneedle array is disposed on a bottom side of the backing; Wherein a user-applied force on the backing effectively separates the backing from the housing and inserts the microneedle array into biological tissue at a predetermined speed.

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

22. The system of claim 19, wherein: The backing comprises: a top portion on which the user-applied force is applied; a middle portion configured to releasably attach the backing to the housing; and A bottom portion, wherein the microneedle array is disposed on a bottom side of the bottom portion of the backing.

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

24. The system of claim 22, wherein: The intermediate portion includes a predefined breaking region configured to fail when the user-applied force is applied to the backing, thereby triggering the separation and insertion.

25. The system of claim 19, wherein: The backing comprises: a top portion on which the user-applied force is applied; and A bottom portion includes a predefined breaking area configured to fail when the user-applied force is applied to the backing, thereby triggering the separation and insertion.

26. The system of claim 19, wherein: The intermediate portion includes a predefined breaking region configured to fail when the user-applied force is applied to the backing, thereby triggering the separation and insertion.

27. The system of claim 19, wherein: The backing is releasably attached to the housing via a predefined breaking region, the predefined breaking region being configured to fail when the user-applied force is applied to the backing, thereby triggering the separation and insertion.

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

29. The system of claim 28, wherein: The tissue support portion is connected to the housing and defines a gap therebetween to accommodate the biological tissue.

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

31. A method comprising: positioning a base of an applicator tool against a target tissue surface, wherein an array of microneedles extends from the applicator disposed in a pre-fire position within the base, wherein the microneedles face the target tissue surface and are separated from the target tissue surface by a spacing distance of at least 5 mm; manually applying a force exceeding a predetermined threshold to the upper surface of the applicator tool, causing a release mechanism connecting the applicator to the base to trigger and release the microneedle and at least a portion of the applicator, thereby driving the microneedle along a guide path toward the tissue surface via the manually applied force at a force and speed effective to insert the microneedle into the skin or other biological tissue, Wherein the triggering of the release mechanism comprises (i) mechanical rupture of a structure securing the applicator in the pre-fire position, or (ii) deformation of the latch feature.

32. The method according to claim 31, wherein: The speed is between about 1 m / s and about 15 m / s, preferably about 8 m / s.

33. The method according to claim 31 or 32, wherein: The spacing distance is 5 mm to 3 cm, preferably about 15 mm.

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

35. The method according to any one of claims 31 to 33, wherein: The release mechanism connecting the applicator to the base includes forces incident upon the arrangement and dimensions of the applicator and base to maintain the applicator in contact with the base without adhesion or integral connection.

36. A device for applying microneedles to skin or other biological tissue, the device comprising: an applicator comprising a microneedle array; as well as a trigger mechanism operably connected to the applicator, wherein the device is configured to apply the microneedle array to the skin at a controlled speed, force and angle, and Wherein the device has no stored energy and the trigger mechanism does not allow the microneedle array to move toward the skin until a threshold manual force is applied to the device.

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

38. The device according to claim 36, wherein At the position, the microneedles are spaced a distance from the skin.

39. The device according to claim 36, wherein: The distance is about 5 mm to about 3 cm, preferably about 15 mm.

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