Development of Redox-Active Nanocomposite Hydrogels for Continuous and Wearable Health Monitoring

可穿戴健身追踪器使用户能够通过实时提供有关其活动、睡眠和静息心率的信息来深入了解其身体健康状况。能够监测和管理癌症、心血管和自身免疫性疾病等慢性疾病的类似设备将通过在需要时为患者提供健康数据来彻底改变医学。已经开发了这样的装置，例如葡萄糖仪，但是它们限于检测可以使用电分析方法通过目标生物标志物（代谢物）的生物催化转化或电位测定法（离子）直接测量的分析物。关于能够非侵入性监测在靶存在下不直接产生电化学信号的生物标志物的可穿戴设备的报道有限。这主要是由于缺乏用于生物标志物如蛋白质、核酸和微生物（例如细菌）的可用无试剂测定。用于便携式检测这些生物标志物的大多数策略依赖于使用外部报告分子和/或试剂，需要单独的靶标记步骤或样品生物流体的预处理。此外，大多数技术仅限于在一个时间点检测单个生物分子，并且在操作过程中极易受到生物污染。 我的研究计划的总体目标是通过开发新的无试剂传感功能材料，实现对代谢物和离子以外的目标分析物的可穿戴监测。我的研究小组将专注于开发新的电化学策略，因为它们非常适合转化为可穿戴监测应用。我们的方法将植根于材料科学：而不是使用氧化还原标记的生物分子作为识别元素，我们将探索使用氧化还原活性（或赝电容）水凝胶对目标生物标志物进行灵敏和无试剂监测。先前的电化学检测策略使用伪电容凝胶用于基于在分析物存在下峰电流的放大的生物标志物的伏安检测。然而，它们仅限于用赝电容转换元件检测参与氧化还原循环的生物分子。拟议的工作将绕过这一限制，通过调查一个以前未开发的检测机制的基础上测量的面积电容的变化，使用循环伏安法。此外，我们将研究调整水凝胶化学和表面形貌的效果，以获得抗生物污染的表面，并可以部署在未处理的样品基质中。这项工作将使所有加拿大人受益，最终导致可穿戴工具的存在，这将消除对侵入性样本收集，昂贵设备的需要，以及诊断和管理致命或慢性疾病的漫长等待时间。

Wearable fitness trackers have enabled users to gain insight into their physical health by providing information regarding their activity, sleep, and resting heart rate in real-time. Analogous devices capable of monitoring and managing chronic illnesses such as cancer, cardiovascular, and autoimmune disease would revolutionize medicine by providing patients access to their health data at the point-of-need. Such devices, for example glucose meters, have been developed, but they are limited to detection of analytes that can be directly measured using electroanalytical methods through biocatalytic conversion of the target biomarker (metabolites) or potentiometry (ions). There are limited reports of a wearable device capable of noninvasive monitoring of biomarkers that do not directly produce an electrochemical signal in the presence of target. This is primarily due to the lack of available reagentless assays for biomarkers such as proteins, nucleic acids, and microoorganisms (e.g. bacteria). Most strategies used for portable detection of these biomarkers rely on the use of external reporter molecules and/or reagents, require a separate target-labelling step, or pre-processing of the sample biofluid. Furthermore, the majority are limited to detection of a single biomolecule at one point in time and are highly susceptible to biofouling during operation. The overarching objective of my research program is to enable wearable monitoring of target analytes beyond metabolites and ions by developing new functional materials for reagent-free sensing. My research group will focus on developing new electrochemical strategies, as they are well-suited for translation to wearable monitoring applications. Our approach will be rooted in materials science: rather than using redox-labelled biomolecules as recognition elements, we will explore the use of redox-active (or pseudocapacitive) hydrogels for sensitive and reagentless monitoring of target biomarkers. Previous electrochemical detection strategies used pseudocapacitive gels for voltammetric detection of biomarkers based on amplification of peak current in the presence of analyte. However, they were limited to detection of biomolecules that participated in redox-cycling with the pseudocapacitive transducing element. The proposed work will circumvent this limitation by investigating a previously-unexplored mechanism of detection based on measuring changes in the areal capacitance using cyclic voltammetry. In addition, we will study the effect of tuning both hydrogel chemistry and surface topography, to obtain a surface that is resistant to biofouling and can be deployed in unprocessed sample matrices. This work will benefit all Canadians by ultimately leading to the existence of wearable tools that will eliminate the need for invasive sample collection, expensive equipment, and long wait times for the diagnoses and management of deadly or chronic diseases.