High-Density Microneedle Array-Based Wearable Electrochemical Biosensor for Detection of Insulin in Interstitial Fluid

Abstract

The development of point-of-care wearable devices capable of measuring insulin concentration has the potential to significantly improve diabetes management and life quality of diabetic patients. However, the lack of a suitable point-of-care device for personal use makes regular insulin level measurements challenging, in stark contrast to glucose monitoring. Herein, we report an electrochemical transdermal biosensor that utilizes a high-density polymeric microneedle array (MNA) to detect insulin in interstitial fluid (ISF). The biosensor consists of gold-coated polymeric MNA modified with an insulin-selective aptamer, which was used for extraction and electrochemical quantification of the insulin in ISF. In vitro testing of biosensor, performed in artificial ISF (aISF), showed high selectivity for insulin with a linear response between 0.01 nM to 4 nM (sensitivity of ∼65 Ω nM-1), a range that covers both the physiological and the pathological concentration range. Furthermore, ex vivo extraction and quantification of insulin from mouse skin showed no impact on the biosensor's linear response. As a proof of concept, an MNA-based biosensing platform was utilized for the extraction and quantification of insulin on live mouse skin. In vivo application showed the ability of MNs to reach ISF, extract insulin from ISF, and perform electrochemical measurements sufficient for determining insulin levels in blood and ISF. We believe that our MNA-based biosensing platform based on extraction and quantification of the biomarkers will help move insulin assays from traditional laboratory approaches to personalized point-of-care settings.