Cell and fluid sampling microneedle patches for monitoring skin-resident immunity

A minimally invasive microneedle device allows repeated sampling of tissue-resident immune cell populations from the skin. Tissues are the window into the immune system Immune status and responses are often determined by analyzing circulating cells isolated from the blood. However, many immune processes and diseases depend on tissue-resident immune cells acting in target organs, which would not be reflected in peripheral immune cells. To sample these tissue-resident cells, Mandal et al. designed a microneedle array that can be applied to the skin. These microneedles can be loaded with adjuvants and antigens of interest to draw in responding immune cells. The microneedles are noninvasive and can be used to follow immune responses over time; similar sampling could be done in the future for other tissues. Tools such as these microneedles can help scientists gain a more accurate understanding of immune responses. Important cell populations reside within tissues and are not accessed by traditional blood draws used to monitor the immune system. To address this issue at an essential barrier tissue, the skin, we created a microneedle-based technology for longitudinal sampling of cells and interstitial fluid, enabling minimally invasive parallel monitoring of immune responses. Solid microneedle projections were coated by a cross-linked biocompatible polymer, which swells upon skin insertion, forming a porous matrix for local leukocyte infiltration. By embedding molecular adjuvants and specific antigens encapsulated in nanocapsules within the hydrogel coating, antigen-specific lymphocytes can be enriched in the recovered cell population, allowing for subsequent detailed phenotypic and functional analysis. We demonstrate this approach in mice immunized with a model protein antigen or infected in the skin with vaccinia virus. After vaccination or infection, sampling microneedles allowed tissue-resident memory T cells (TRMs) to be longitudinally monitored in the skin for many months, during which time the antigen-specific T cell population in systemic circulation contracted to low or undetectable counts. Sampling microneedles did not change the immune status of naïve or antigen-exposed animals. We also validated the ability of cell sampling using human skin samples. This approach may be useful in vaccines and immunotherapies to temporally query TRM populations or as a diagnostic platform to sample for biomarkers in chronic inflammatory and autoimmune disorders, allowing information previously accessible only via invasive biopsies to be obtained in a minimally invasive manner from the skin or other mucosal tissues.