Collaborative Research: Injectable, Biocompatible, Programmed-Bioresorbable Nanosensor Array for Continuous Glucose Monitoring

糖尿病是一种代谢紊乱和主要的世界健康问题。据国际糖尿病联合会称，全世界有超过3.5亿糖尿病患者，每年造成320多万人死亡。因此，葡萄糖检测在糖尿病的诊断和治疗中是至关重要的。该项目将说明如何将纳米技术、生物材料和生物传感技术结合在一起，形成可注射的、生物相容的、生物可吸收的纳米传感器阵列，用于连续血糖监测。这项工作将推动体外和/或体内连续血糖监测技术的发展，如果成功，不仅将对公众健康产生巨大影响，而且还将提供从基础科学到应用的示范。该项目将通过将先进的生物传感技术整合到研究生、本科生和高中生的教育和实验室培训中来影响他们的教育，并通过康涅狄格大学和东北大学内外的各种外展活动积极与公众和行业公司互动。此外，还开设了生物分析传感器课程。这个多学科的提案旨在开发一种可注射的生物相容性和程序化生物可吸收的表面增强拉曼散射传感器，用于长期、皮下、连续的血糖监测。许多跨越生物、纳米、材料和传感技术的新特征将无缝地融入这种新型葡萄糖传感系统。制备了一种三明治状的葡萄糖传感材料，包括可编程的生物可吸收的葡萄糖响应纳米传感器阵列，该纳米传感器阵列由生物相容性和生物可降解的水凝胶覆盖，并包裹有抗炎药。然后使用灭菌的留置针将制备好的传感器皮下递送，用于长期、连续的葡萄糖检测。我们将系统地研究其传感性能。(1)水凝胶良好的生物相容性和生物降解性，以及(2)纳米传感器阵列良好的生物相容性和稳定性，(3)长期使用后传感材料可编程的生物可吸收性，(4)葡萄糖与传感材料的特异性和可变性结合，以及传感材料独特而强烈的葡萄糖响应光信号，区别于皮肤组织和水凝胶，(5)通过拉曼散射进行无创监测，(6)水凝胶包裹消炎药的抗炎作用；(7)方便穿皮的传感器微创输送，实现长期可靠连续血糖监测。

Diabetes is a metabolic disorder and major world health problem. As stated by the International Diabetes Federation, there are over 350 million diabetics worldwide causing over 3.2 million deaths annually. Consequently, glucose detection is of paramount importance in the diagnosis and treatment of diabetes. This project will illustrate how nanotechnology, biomaterials, and biosensing technologies can be meshed together for injectable, biocompatible, bioresorbable nanosensor array for continuous glucose monitoring. The work will advance in vitro and/or in vivo monitoring technology for continuous glucose monitoring in general and, if successful, will not only have an enormous impact on public health, but also provide a demonstration from basic science to applications. This project will impact education of the graduate, undergraduate and high school students by integrating advanced biosensing into their educational and laboratory training, and actively interact with the general public and industry companies through various outreach activities within and outside of the University of Connecticut and Northeastern University. Moreover, a new course of Bioanalytical Sensor will be offered to students. This multidisciplinary proposal aims to develop an injectable biocompatible and programmed-bioresorbable surface-enhanced Raman scattering sensor for long-term, subcutaneous, continuous glucose monitoring. A number of novel features crossing bio-, nano-, material- and sensing technologies will be seamlessly meshed into this novel glucose sensing system. A sandwich-like glucose sensing material, including programmed-bioresorbable glucose-responsive nanosensor array covered by biocompatible and biodegradable hydrogel with entrapped anti-inflammatory drug, will be fabricated. Then a sterilized indwelling needle will be used to deliver the as-prepared sensor subcutaneously for long-term, continuous glucose sensing. The sensing performance will be systematically investigated. The synergistic effects of (1) good biocompatibility and biodegradability of hydrogel, together with (2) good biocompatibility and stability of nanosensor array, (3) programmable bioresorbability of sensing materials after long-term use, (4) specific and reversible binding of glucose with sensing material and its unique and strong glucose-responsive optical signals distinguishable from those of skin tissue and hydrogel, (5) non-invasive monitoring through Raman scattering, (6) anti-inflammatory effect provided by anti-inflammatory drug entrapped in hydrogel, and (7) minimally invasive delivery of sensor through convenient skin piercing, will accomplish the goal of reliable long-term continuous glucose monitoring.