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Fully integrated wearable microneedle biosensing platform for wide-range and real-time continuous glucose monitoring

葡萄糖氧化酶 连续血糖监测 生物传感器 材料科学 戊二醛 普鲁士蓝 生物医学工程 可穿戴计算机 纳米技术 小型化 线性范围 持续监测 电极 计算机科学 电化学 嵌入式系统 检出限 化学 医学 胰岛素 色谱法 运营管理 物理化学 内分泌学 经济 血糖性
作者
Lei Li,Yujie Zhou,Chenwei Sun,Zhengming Zhou,Jieyu Zhang,Yuanyuan Xu,Xuanyu Xiao,Hui Deng,Yuting Zhong,Guoyuan Li,Zhiyu Chen,Wei Deng,Xuefeng Hu,Yunbing Wang
出处
期刊:Acta Biomaterialia [Elsevier BV]
卷期号:175: 199-213 被引量:20
标识
DOI:10.1016/j.actbio.2023.12.044
摘要

Wearable microneedle sensors for continuous glucose monitoring (CGM) have great potential for clinical impact by allowing access to large data sets to provide individualized treatment plans. To date, their development has been challenged by the accurate wide linear range tracking of interstitial fluid (ISF) glucose (Glu) levels. Here, we present a CGM platform consisting of a three-electrode microneedle electrochemical biosensor and a fully integrated radio-chemical analysis system. The long-term performance of the robust CGM on diabetic rats was achieved by electrodepositing Prussian blue (PB), and crosslinking glucose oxidase (GOx) and chitosan to form a 3D network using glutaraldehyde (GA). After redox by GOx, PB rapidly decomposes hydrogen peroxide and mediates charge transfer, while the 3D network and graphite powder provide enrichment and release sites for Glu and catalytic products, enabling a sensing range of 0.25–35 mM. Microneedle CGM has high sensitivity, good stability, and anti-interference ability. In diabetic rats, CGM can accurately monitor Glu levels in the ISF in real-time, which are highly consistent with levels measured by commercial Glu meters. These results indicate the feasibility and application prospects of the PB-based CGM for the clinical management of diabetes. This study addresses the challenge of continuous glucose monitoring system design where the narrow linear range of sensing due to the miniaturization of sensors fails to meet the monitoring needs of clinical diabetic patients. This was achieved by utilizing a three-dimensional network of glutaraldehyde cross-linked glucose oxidase and chitosan. The unique topology of the 3D network provides a large number of sites for glucose enrichment and anchors the enzyme to the sensing medium and the conductive substrate through covalent bonding, successfully blocking the escape of the enzyme and the sensing medium and shortening the electron transfer and transmission path.
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