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.

中文翻译：

---

基于生物材料的可插入式多分析物条形码传感器，用于连续监测葡萄糖和氧气


慢性病，包括糖尿病、心血管疾病和微血管并发症，对全球发病率和死亡率有重大影响。目前的监测工具，如血糖仪和连续血糖监测仪，只测量一种分析物;多重检测技术为监测多种生物标志物提供了一种很有前途的方法，能够管理合并症并提供更全面的疾病见解。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比例的耗氧量，以及使用基于寿命的探针对组织氧的磷光报告。该传感器经过专门设计，可在溶解氧含量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，该水凝胶具有四个独立的隔室，分别填充有葡萄糖或氧感应磷光微粒。我们评估了在低氧条件下条形码水凝胶对生理范围内葡萄糖水平波动的响应，证明了动态范围和灵敏度的受控调整。此外，条形码传感器在 12 周内表现出卓越的储存稳定性，并且在近 50 个器件中表现出完全可逆性和出色的重现性（磷光寿命变化 ∼6%）。电子束灭菌对条形码传感器的葡萄糖反应的影响可以忽略不计。 此外，我们的调查显示，当受到交替葡萄糖浓度（0 和 200 mg/dL）时，氧室中的磷光寿命变化最小，同时葡萄糖反应室的寿命增加，展示了传感器的多分析物传感能力，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，并且在数月内具有出色的材料稳定性。这些发现支持进一步开发类似的技术，以引入针对多种生物标志物的光学检测，这些技术可以向个人提供持续或按需的反馈以管理慢性病。