An aptamer-responsive microneedle patch sensor platform combining with hybridization chain reaction amplification for detection of steroid hormone cortisol in skin interstitial fluid.

Fluctuations in cortisol levels from stressors are critical for the evaluation of endocrine function in body, and abnormal levels of cortisol may indicate serious health risks. Common strategies for cortisol detection are limited by the drawbacks of the intricate and time-consuming operations and the generation of body trauma. Herein, an aptamer-responsive microneedle patch sensor combining with hybridization chain reaction (HCR) amplification (Apt-HCR MN COR patch) was prepared for easy, accurate and minimally-invasive detection of cortisol in skin interstitial fluid (ISF). In this microneedle patch, swellable methacrylated hyaluronic acid (MeHA) was employed as the matrix for ISF extraction and probes loading. When cortisol bound its aptamer, the trigger DNA initiated the HCR in microneedle patch, producing a fluorescent signal proportional to the cortisol content. Under optimized conditions, in vitro and in vivo investigation confirmed the feasibility of the Apt-HCR MN COR patch for cortisol assay, and good biocompatibility was demonstrated. Benefiting from the aptamer recognition and HCR amplification, the Apt-HCR MN COR patch exhibited excellent selectivity and a detection limit (LOD = 0.048 μM) which could cover cortisol levels in ISF. As a proof of concept, after the established mouse model had shown a circadian rhythm of cortisol secretion, the patch was further used to track cortisol response in short duration of running fatigue exercise on this mouse model. It was demonstrated the detection results agreed well with those obtained by the classical enzyme-linked immunosorbent assay (ELISA). We believed that this strategy will inspire the development of MN sensors for cortisol-related disorders monitoring.