A cold atmospheric plasma (CAP)-mediated ICB therapy/delivery device are disclosed herein that employs a patch having microneedles that are used to deliver the CAP transdermally along with an immune checkpoint inhibitor for enhancing transdermal treatment efficacy. The hollow-structured microneedle patch can facilitate the transportation of CAP through the skin, causing tumor cell death. The release of cancer antigens then promotes the maturation of dendritic cells in the tumor-draining lymph nodes, subsequently initiating the T cell-mediated immune response. Anti-PDL1 antibody (aPDL1), an immune checkpoint inhibitor (or other immune checkpoint inhibitors), released from the microneedle patch (in some embodiments) further augments the anti-tumor immunity. The transdermal combinational CAP and ICB therapy inhibits tumor growth for both primary tumors as well as distant tumors, with prolonged survival in the tumor-bearing mice. Such results should translate to other species.

Disclosed is a microneedling device and a method for the microneedling of human or animal tissue. The method comprises the following steps; (a) providing a microneedling device having an electrically conductive microneedle and an electrically conducting nosepiece assembly spaced apart from the electrically conductive microneedle and acting as a counter electrode; (b) placing the electrically conductive microneedle and nosepiece assembly into contact with the tissue to be microneedled; (c) measuring the electrical impedance between the microneedle tip and the nosepiece or the current through the microneedle motor; (d) commencing insertion of the microneedle and moving the microneedle toward the tissue surface; (e) starting a step counter when the impedance reduces or the microneedle motor current increases; (f) incrementing the step counter with every step of the vertical drive motor until the step count reaches the prespecified value thereby controlling the depth of the hole microneedled.

The present invention provides for microneedle arrays and related systems and methods. Particularly, microneedle arrays that are configured to deliver active agents, including nucleic acids and vaccines, are provided. Additional related methods of vaccinating and minimizing the amount of vaccine necessary for effective inoculation are also provided.

An applicator and method for applying a microneedle device to a skin surface. The applicator can include a first portion comprising a microneedle array, and a second portion coupled to the first portion via a connector. The connector can be configured to yield or fracture by changing from a first state in which the connector is intact to a second state in which the connector is yielded or fractured when a threshold application force is applied to at least one of the first portion and the second portion in a direction substantially perpendicular with respect to the first portion. The method can include pressing the applicator in a direction substantially perpendicular to the first portion to press the microneedle array into the skin surface until the threshold application force is met or exceeded and the connector is changed to its second state.

A method of forming an implant in the tissue can include: providing an injectable composition having a neat liquid carrier, wherein the neat liquid carrier is substantially liquid at room temperature and/or about body temperature; and injecting the neat liquid solution into the tissue at the rate of 10-12000 injections per minute and/or at an amount of 1.0E-02 ml to 1.0E-16 ml per needle per injection. The neat liquid carrier can be polymeric or non-polymeric. The neat liquid carrier can be biodegradable. The neat liquid carrier can include a viscosity-modifying agent. The injecting can form an implant with area greater than or equal to 5 mm.sup.2. The neat liquid carrier can be injected at a depth of 10 microns to 5 mm. The neat liquid solution can include a drug or other agent.

A transdermal drug delivery device comprises needles for piercing the skin of a patient to form pores in a predefined pattern; and carriers in the same pattern that may be loaded with a drug for delivery. The carriers are applied to the pores to deliver the drug through the pores to a location beneath the surface of the skin. The carriers may remain outside the pores, be introduced into the pores after the needles have been removed, or be inserted alongside the needles while they are still in place.

An article (100) comprising at least one microneedle (160) is provided. The article comprises a first side (112) and a second side (114) opposite the first side. The first side comprises a central cavity portion (120) and a platform portion (130), with at least one microneedle extending therefrom, wherein the platform portion is not coplanar with the central cavity portion. The platform portion substantially surrounds the central cavity portion. The at least one microneedle comprises a body comprising an outer surface (163); a base segment (166) having a base (162) and a first shape; a tip segment (168) having a tip and a second shape, wherein the second shape is distinct from the first shape; a transition plane (167) that delineates the base segment and the tip segment; and a central axis (180). Methods of using the article are also provided.

The present invention generally relates to collecting, determining and/or transmitting information associated with the process of receiving bodily fluid through a device opening and/or delivering substances to a subject. In one aspect, the device includes an information collecting portion and a fluid receiving portion. In another aspect, the two portions are constructed and designed to attach to one another. In one embodiment, actuation of one of the portions causes the other portion to actuate. Methods of time keeping and information transmission are also discussed.

The present disclosure relates generally to devices, systems, and methods for diagnosis and treatment via laser-treated skin and, more particularly, to devices, systems, and methods for inducing leakage or rupture of one or more blood vessels comprising the dermis for various diagnostic and therapeutic applications. Other aspects of the present disclosure can include methods for detecting one or more target analytes in a dermis of a subject, methods for facilitating skin-to-blood delivery of agent in a subject, and methods for collecting a fluid sample from the dermis of a subject.

Embodiments include devices and methods configured to fractionally resect skin and/or fat. Fractional resection is applied as a stand-alone procedure in anatomical areas that are off-limits to conventional plastic surgery due to the poor tradeoff between the visibility of the incisional scar and amount of enhancement obtained. Fractional resection is also applied as an adjunct to established plastic surgery procedures such as liposuction, and is employed to significantly reduce the length of incisions required for a particular application. The shortening of incisions has application in both the aesthetic and reconstructive realms of plastic surgery.