Department of Biomedical Engineering, Texas A&M University, College Station, Texas 77843, United States.
Electrical & Computer Engineering Department, University of California, Los Angeles, California 90095, United States.
ACS Sens. 2024 Nov 22;9(11):6060-6070. doi: 10.1021/acssensors.4c01926. Epub 2024 Nov 4.
Chronic diseases, including diabetes, cardiovascular diseases, and microvascular complications, contribute significantly to global morbidity and mortality. Current monitoring tools such as glucometers and continuous glucose monitors only measure one analyte; multiplexing technologies offer a promising approach for monitoring multiple biomarkers, enabling the management of comorbidities and providing more comprehensive disease insights. In this work, we describe a miniaturized optical "barcode" sensor with high biocompatibility for the continuous monitoring of glucose and oxygen. This enzymatic sensor relies on oxygen consumption in proportion to local glucose levels and the phosphorescence reporting of tissue oxygen with a lifetime-based probe. The sensor was specifically designed to operate in a tissue environment with low levels of dissolved oxygen. The barcode sensor consists of a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with four discrete compartments separately filled with glucose- or oxygen-sensing phosphorescent microparticles. We evaluated the response of the barcode hydrogels to fluctuating glucose levels over the physiological range under low oxygen conditions, demonstrating the controlled tuning of dynamic range and sensitivity. Moreover, the barcode sensor exhibited remarkable storage stability over 12 weeks, along with full reversibility and excellent reproducibility (∼6% variability in the phosphorescence lifetime) over nearly 50 devices. Electron beam sterilization had a negligible effect on the glucose response of the barcode sensors. Furthermore, our investigation revealed minimal phosphorescence lifetime changes in oxygen compartments while exhibiting increased lifetime in glucose-responsive compartments when subjected to alternating glucose concentrations (0 and 200 mg/dL), showcasing the sensor's multianalyte sensing capabilities without crosstalk between compartments. Additionally, the evaluation of chronic tissue response to sensors inserted in pigs revealed the appropriate biocompatibility of the barcodes as well as excellent material stability over many months. These findings support further development of similar technologies for introducing optical assays for multiple biomarkers that can provide continuous or on-demand feedback to individuals to manage chronic conditions.
慢性疾病，包括糖尿病、心血管疾病和微血管并发症，是全球发病率和死亡率的主要原因。目前的监测工具，如血糖仪和连续血糖监测器，仅测量一种分析物；多重分析技术为监测多种生物标志物提供了有前途的方法，使共病的管理成为可能，并提供更全面的疾病洞察。在这项工作中，我们描述了一种具有高生物相容性的小型化光学“条形码”传感器，用于连续监测葡萄糖和氧气。这种酶传感器依赖于与局部葡萄糖水平成正比的氧气消耗，以及基于寿命的探针对组织氧的磷光报告。该传感器专门设计用于在溶解氧水平低的组织环境中运行。条形码传感器由聚乙二醇二丙烯酸酯（PEGDA）水凝胶组成，其中四个分立隔室分别填充有葡萄糖或氧感应磷光微球。我们评估了条形码水凝胶在低氧条件下对生理范围内波动葡萄糖水平的响应，证明了动态范围和灵敏度的可控调谐。此外，条形码传感器在 12 周的时间内表现出显著的存储稳定性，并且在近 50 个设备上具有完全的可逆性和出色的重现性（磷光寿命的变化约为 6%）。电子束灭菌对条形码传感器的葡萄糖响应几乎没有影响。此外，我们的研究表明，当受到交替葡萄糖浓度（0 和 200mg/dL）的影响时，氧隔室中的磷光寿命变化最小，而在葡萄糖响应隔室中的磷光寿命增加，展示了传感器的多分析物传感能力，而隔室之间没有串扰。此外，对插入猪体内的传感器的慢性组织反应的评估表明，条形码具有适当的生物相容性，并且在数月的时间内具有优异的材料稳定性。这些发现支持进一步开发类似的技术，以引入用于多种生物标志物的光学分析，为个体提供连续或按需反馈，以管理慢性疾病。
