Dervisevic Muamer, Esser Lars, Chen Yaping, Alba Maria, Prieto-Simon Beatriz, Voelcker Nicolas H
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia; Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, Victoria, 3168, Australia.
Commonwealth Scientific and Industrial Research Organization (CSIRO, Clayton, Victoria, 3168, Australia.
Biosens Bioelectron. 2025 Mar 1;271:116995. doi: 10.1016/j.bios.2024.116995. Epub 2024 Nov 26.
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 and 4 nM (sensitivity of ∼65 Ω nM), 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.
能够测量胰岛素浓度的即时检测可穿戴设备的开发，有潜力显著改善糖尿病管理及糖尿病患者的生活质量。然而，缺乏适合个人使用的即时检测设备使得定期测量胰岛素水平具有挑战性，这与血糖监测形成鲜明对比。在此，我们报告一种电化学透皮生物传感器，其利用高密度聚合物微针阵列（MNA）来检测间质液（ISF）中的胰岛素。该生物传感器由涂金的聚合物MNA组成，其用胰岛素选择性适配体修饰，用于ISF中胰岛素的提取和电化学定量。在人工间质液（aISF）中进行的生物传感器体外测试显示对胰岛素具有高选择性，在0.01 nM至4 nM之间呈线性响应（灵敏度约为65 Ω nM），该范围涵盖生理和病理浓度范围。此外，从小鼠皮肤进行胰岛素的离体提取和定量显示对生物传感器的线性响应无影响。作为概念验证，基于MNA的生物传感平台用于在活小鼠皮肤上提取和定量胰岛素。体内应用表明微针能够到达ISF，从ISF中提取胰岛素，并进行足以测定血液和ISF中胰岛素水平的电化学测量。我们相信，我们基于提取和定量生物标志物的基于MNA的生物传感平台将有助于将胰岛素检测从传统实验室方法转变为个性化即时检测设置。
