Hydrogel microneedle based transdermal fluorescent patch for the on-site and non-invasive diagnosis of Alzheimer's disease.

Detection of biomarkers in interstitial fluid (ISF) by microneedles (MNs) has received extensive attentions as a non-invasive biosensing strategy. However, fewer work has focused on the long non-coding RNAs (lncRNAs) sensing, which are most likely present in ISF and engage in the occurrence and development of Alzheimer's disease (AD). In this work, taking adenocarcinoma transcript 1 (MALAT1) as the representative of lncRNAs, which is abnormally down-regulated in AD patients, a robust hydrogel MN array - based fluorescent patch was developed for MALAT1 by integrating a methacrylated gelatin (GelMA) hydrogel MN as the extraction tool with a strand displacement reaction (SDR) mediated fluorescent probe. Specifically, the MNs were prepared by the simple and feasible photo-crosslinking of GelMA, which displayed satisfactory swelling capability for extracting ISF and mechanical strength to penetrate the skin's cuticle layer. Subsequently, a triplex SDR amplification probe was constructed for MALAT1 sensing. By mixing with the prepolymer solution, the MNs patch loaded with the fluorescent probe was fabricated, which demonstrated excellent sensing performances in both PBS and agarose simulated skin, with lower limits of quantification (LLOQ) of 7.62 and 13.24 nM, respectively. The developed MN patch was proved highly suitable for distinguishing the down-regulated MALAT1 expressions in ISF of AD mice. This work represented the first example to correlate the changes in the levels of MALAT1 in ISF with AD pathology, providing a practical tool for the early non - invasive diagnosis of AD.