Self-Cleaning Sensor Membranes to Improve Glucose Monitoring In Vivo

描述（由申请人提供）：糖尿病是一个国际性的健康问题，全世界有数百万患者。开发一种快速方便的监测糖尿病患者血糖的生物传感器技术是一个尚未满足的需求。因此，本研究的特定目标是开发一种自清洁水凝胶传感器膜，该膜可以周期性地、热驱动地去除粘附细胞，以提高植入葡萄糖传感器的功效和寿命。植入式光学传感器具有连续检测分析物（如葡萄糖）的潜力。然而，作为宿主反应的一部分，感知常常受到周围组织细胞的附着和积累的损害。结果，葡萄糖扩散减弱，传感器必须移除并更换。我们将开发一种新型的自清洁热响应纳米复合水凝胶膜，这种膜以中空管的形式制成，可以进行荧光葡萄糖反应试验。传感器将被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与开发的光学系统照射时，提供与葡萄糖浓度成正比的荧光峰的连续测量。本研究提出了三个具体目标：(1)迭代开发热响应性纳米复合水凝胶传感器膜，并表征其力学性能以及热调节的膨胀/驻留行为、表面亲水性/疏水性、葡萄糖扩散和细胞释放行为；(2)迭代评估选定的热响应性纳米复合水凝胶传感器膜的功效，以进行葡萄糖响应实验；(3)在正常大鼠和糖尿病大鼠中，量化由选择的含有葡萄糖反应试验的自清洁水凝胶膜制备的传感器的体内功效。来自德克萨斯农工大学生物医学和化学工程系的多学科团队代表的设施和个人非常适合开展这项研究，并且在热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。该团队具有合作历史，并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：根据世界卫生组织的数据，糖尿病是一种使人衰弱的慢性疾病，影响着1.8亿多人，预计到2030年将达到3.66亿人。这种疾病要求病人每天多次监测血糖水平。这种监测目前是非连续的，主要通过市售的手指或前臂棒法血糖读数装置进行。因此，这项工作的最终目标是开发一种可植入的自清洁葡萄糖传感器，一旦植入，就可以使用手表式设备的光来连续监测血糖，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.