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

可穿戴式健身追踪器通过实时提供有关活动、睡眠和静息心率的信息，使用户能够了解自己的身体健康状况。类似的设备能够监测和管理慢性疾病，如癌症、心血管疾病和自身免疫性疾病，通过为患者提供在需要时访问其健康数据的途径，将彻底改变医学。这样的设备，例如血糖仪，已经被开发出来，但它们仅限于检测可以通过目标生物标志物（代谢物）或电位测定法（离子）的生物催化转化使用电分析方法直接测量的分析物。关于能够无创监测生物标志物的可穿戴设备的报道有限，这些生物标志物在目标存在时不直接产生电化学信号。这主要是由于缺乏可用于生物标志物（如蛋白质、核酸和微生物（如细菌））的无试剂测定方法。用于便携式检测这些生物标志物的大多数策略依赖于外部报告分子和/或试剂的使用，需要单独的目标标记步骤，或对样品生物液进行预处理。此外，大多数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的影响。我的研究计划的总体目标是通过开发用于无试剂传感的新功能材料，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件，我们将探索使用氧化还原活性（或假电容）水凝胶对目标生物标志物进行敏感和无试剂监测。以前的电化学检测策略使用假电容凝胶进行生物标志物的伏安检测，基于在分析物存在下的峰值电流放大。然而，它们仅限于检测与假电容转导元件一起参与氧化还原循环的生物分子。提出的工作将通过研究以前未探索的基于使用循环伏安法测量面电容变化的检测机制来绕过这一限制。此外，我们将研究调整水凝胶化学和表面形貌的影响，以获得抗生物污垢的表面，并可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，这些工具将消除对侵入性样本收集、昂贵设备的需求，以及对致命或慢性疾病的诊断和管理的长时间等待。

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.