Self-Cleaning Sensor Membranes to Improve Glucose Monitoring In Vivo

描述（由申请人提供）：糖尿病是一个国际健康问题，全球有数百万患者。存在开发一种生物传感器技术的未满足的需求，该生物传感器技术是监测糖尿病患者的血糖的快速且方便的方式。因此，本研究的特定目标是开发自清洁水凝胶传感器膜，其经历粘附细胞的循环、热驱动去除，以提高植入的葡萄糖传感器的功效和寿命。植入的基于光学的传感器具有连续检测分析物（例如葡萄糖）的潜力。然而，作为宿主反应的一部分，来自周围组织的细胞的附着和积累通常会损害传感。因此，葡萄糖扩散减少，必须移除并更换传感器。我们将开发新型自清洁温敏纳米复合水凝胶膜，该膜以中空管的形式制造，该中空管容纳荧光葡萄糖响应测定。传感器将植入皮肤下方的组织液中。植入后，葡萄糖特异性传感器将在用开发的光学系统照射时提供与葡萄糖浓度成比例的荧光峰的连续测量。这项研究提出了三个具体目标：（1）迭代地开发温敏纳米复合水凝胶传感器膜并表征其机械性能以及热调节溶胀/去溶胀行为、表面亲水性/疏水性、葡萄糖扩散和细胞释放行为，（2）迭代地评估所选温敏纳米复合水凝胶传感器膜容纳葡萄糖响应测定的功效，和（3）使用正常和糖尿病大鼠，定量由含有葡萄糖响应性测定的所选自清洁水凝胶膜制备的传感器的体内功效。来自德克萨斯A & M大学生物医学和化学工程系的多学科团队中的设施和个人非常适合开展这项研究，并在温敏水凝胶的化学合成，光学和电化学葡萄糖生物传感以及生物医学和化学工程方面具有专业知识。该团队有着悠久的合作历史，在葡萄糖和其他分析物光学传感器的设计和开发方面拥有超过18年的经验。公共卫生相关性：糖尿病是一种使人衰弱的慢性疾病，根据世界卫生组织的数据，影响超过1.8亿人，预计2030年将达到3.66亿人。这种疾病需要患者每天多次监测葡萄糖水平。这种监测目前是不连续的，主要通过使用市售的手指或前臂棒法血糖阅读装置来进行。因此，这项工作的最终目标是开发一种植入式自清洁葡萄糖传感器，一旦植入，可以用于通过手表型设备的光连续监测葡萄糖，以帮助糖尿病患者。

DESCRIPTION (provided by applicant): Diabetes is an international health concern with millions of patients worldwide. There is an unmet need to develop a biosensor technology that is a fast and convenient way to monitor blood glucose in diabetics. Thus, the particular goal of this research is the development of a self-cleaning hydrogel sensor membrane which undergoes cyclical, thermally driven removal of adhered cells to improve the efficacy and lifetime of an implanted glucose sensor. Implanted optically based sensors have the potential for continuous detection of an analyte (e.g. glucose). However, sensing is often compromised by the attachment and accumulation of cells from surrounding tissue as part of the host response. As a result, glucose diffusion is diminished and the sensor must be removed and replaced. We will develop novel self-cleaning thermoresponsive nanocomposite hydrogel membranes fabricated in the form of a hollow tube that houses a fluorescent glucose-responsive assay. The sensor will be implanted in the interstitial fluid just beneath the skin. After implantation, the glucose specific sensor will, when illuminated with the optical system developed, provide continuous measurement of fluorescence peaks that are proportional to the glucose concentration. There are three specific aims proposed in this research: (1) iteratively develop thermoresponsive nanocomposite hydrogel sensor membranes and characterize their mechanical properties as well as thermally-modulated swelling/dewelling behavior, surface hydrophilicity/- hydrophobicity, glucose diffusion and cell-release behavior, (2) iteratively evaluate the efficacy of selected thermoresponsive nanocomposite hydrogels sensor membranes to house a glucose-responsive assay, and (3) quantify the in vivo efficacy of the sensors prepared from selected self-cleaning hydrogel membranes containing the glucose-responsive assay, using both normal and diabetic rats. The facilities and individuals represented in this multidisciplinary team from the Biomedical and Chemical Engineering Departments at Texas A&M University are uniquely suited to carry out this research and have expertise in the chemical synthesis of thermoresponsive hydrogels, optical and electrochemical glucose biosensing, as well as biomedical and chemical engineering. The team has a history of collaboration and brings over 18 years of experience in the design and development of optical sensors for glucose and other analytes. PUBLIC HEALTH RELEVANCE: Diabetes mellitus is a debilitating, chronic, disease that affects over 180 million people, according to the World Health Organization, with estimates projecting to 366 million in 2030. The disease requires the patient to monitor glucose levels several times daily. This monitoring is currently non-continuous and performed primarily by using a commercially available finger or forearm stick method blood glucose reading device. Thus, the ultimate goal of this work is the development of an implantable self-cleaning glucose sensor that, once implanted, could be used to monitor glucose continuously with light from a watch-type of device to help patients with diabetes mellitus.