Crosslinked microneedle patch to extract interstitial fluid for diagnosis

Abstract

Microneedles bring the advantages of being painless, safe and easy to administer. However, current methods of microneedle sampling of the interstitial fluid (ISF) for clinical analysis have long durations of administration (at least an hour), which cause great inconvenience for the patient and often impairs the accuracy of the analysis due to the lag time of the sampling. Hyaluronic acid has the intrinsic ability to bind to large volumes of water. In this study, we have successfully developed a hydrogel microneedle based on hyaluronic acid derivative (methylcrylate modified hyaluronic acid, MeHA) and demonstrated its superior mechanical strength; having approximate 8 times the strength required for penetration into the skin. It was successfully penetrated into porcine cadaver skin, as well as the skin of a live mouse. We have also demonstrated the superior swelling ability and rapid absorption ability of our MeHA microneedle, which could gain almost 10 times its original mass in phosphate buffer saline (PBS) in 2min, while retaining it structural integrity. When only the tips of our microneedle contact water in an agarose hydrogel model, it could absorb approximately 1.5 times its original weight in 10min. After extraction of analytes, we could also easily recover the analytes for analysis by centrifugation with DI water. MeHA microneedles are also biodegradable, biocompatible and non-immunogenic which negates the risk of irritation or inflammation. With more extensive research, the development of the MeHA microneedles that rapidly extract ISF for analysis could potentially open up a wide field of therapeutic options.