A Self-Cleaning Membrane to Extend the Lifetime of an Implanted Glucose Biosensor

自清洁膜可延长植入式葡萄糖生物传感器的使用寿命

• 批准号: 8918591
• 负责人: Melissa Grunlan
• 金额: $ 32.43万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8918591
• 关键词: Affect; Alexa594; Binding Sites; Biological Assay; Biosensor; Blood Glucose; Caliber; Cells; Chronic Disease; Collaborations; Concanavalin A; Detection; Development; Devices; Diabetes Mellitus; Diffusion; Dimensions; Elements; Event; Excision; Exhibits; Failure; Fingers; Fluorescence; Frequencies; Funding; Geometry; Glucose; Goals; Health; Heating; Housing; Hydrogels; Hyperglycemia; Hypoglycemia; Immune response; Implant; In Vitro; Injection of therapeutic agent; International; Length; Marketing; Measures; Mechanics; Medical; Membrane; Methods; Modeling; Monitor; Nature; Optics; Patients; Physiological; Property; Proteins; Rattus; Recording of previous events; Reporting; Research; Signal Transduction; Siloxanes; Site; Source; Subcutaneous Tissue; System; Technology; Testing; Texas; Time; United States National Institutes of Health; Universities; Work; Wrist; base; biomaterial compatibility; compliance behavior; cost; design; diabetic; fluorophore; glucose monitor; implantation; improved; in vivo; innovation; monitoring device; multidisciplinary; nanocomposite; nanoparticle; novel strategies; poly-N-isopropylacrylamide; programs; sensor; subcutaneous

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 continuously monitor blood glucose levels in diabetics. The proposed work seeks to develop an implantable glucose biosensor which can monitor glucose levels over a long period of time (3-6 months). The proposed implanted glucose biosensor design is distinctively different compared to existing continuous glucose monitoring devices (which have a disappointing lifetime of 3-7 days) and is expected to result in improved long-term efficacy. The innovative aspects of the proposed implantable glucose biosensor includes: (1) a self-cleaning membrane, (2) a fluorescent glucose sensing assay which is contained in the membrane to form the biosensor and (3) an end-use biosensor design which enables complete subcutaneous dwelling and convenient glucose monitoring by the patient. Membrane biofouling is considered to be the leading cause of failure for in vivo biosensors. The proposed "self-cleaning" membrane is distinct in its approach to control biofouling; it is designed to display active "self-cleaning" as a result of its thermoresponsive nature. The membrane will be based on a thermoresponsive nanocomposite hydrogel which is thermally cycled via an external heating source. This membrane will be used to house a glucose sensing assay which has been shown to have a larger dynamic range for physiologic glucose levels versus other optical fluorescent glucose sensing methods. Finally, the membrane and sensing assay will be combined to form a biosensor with a cylindrical geometry (expected dimensions of <5 mm diameter and <10 mm length) which permits a convenient end-use design for implantation, replacement and patient glucose monitoring. Ultimately, after injection into the subcutaneous tissue of the wrist, a watch device worn over the implanted biosensor site would contain the optical probe for non-invasive continuous glucose sensing and as well as the thermal heating element for membrane cleaning (i.e. thermal cycling). The multidisciplinary team of Drs. Grunlan, Cote, Clubb and Pishko and the facilities at Texas A&M University will enable the successful completion of the proposed research. The team brings the expertise to develop the proposed membrane and biosensors and conduct the in vitro and in vivo analysis.

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。开发一种生物传感器技术的需求尚未得到满足，这种技术是一种快速、便捷的方法来连续监测糖尿病患者的血糖水平。拟议的工作旨在开发一种可植入的葡萄糖生物传感器，可以长期（3-6 个月）监测血糖水平。与现有的连续血糖监测设备（其使用寿命为 3-7 天，令人失望）相比，所提出的植入式葡萄糖生物传感器设计明显不同，预计将提高长期疗效。所提出的植入式葡萄糖生物传感器的创新方面包括：（1）自清洁膜，（2）荧光葡萄糖传感测定法包含在膜中以形成生物传感器，以及（3）最终用途生物传感器设计，使完整的皮下居住和患者方便的血糖监测。膜生物污染被认为是体内生物传感器失效的主要原因。所提出的“自清洁”膜在控制生物污垢的方法上是独特的；由于其热响应特性，它被设计为具有主动的“自清洁”功能。该膜将基于热响应纳米复合水凝胶，通过外部热源进行热循环。该膜将用于容纳葡萄糖传感测定，与其他光学荧光葡萄糖传感方法相比，该膜具有更大的生理葡萄糖水平动态范围。最后，膜和传感测定将结合起来形成具有圆柱形几何形状的生物传感器（预期尺寸<5毫米直径和<10毫米长度），这允许方便的植入、替换和患者血糖监测的最终用途设计。最终，在注射到手腕的皮下组织后，佩戴在植入的生物传感器部位的手表设备将包含用于非侵入性连续葡萄糖传感的光学探针以及用于膜清洁（即热循环）的热加热元件。博士的多学科团队。 Grunlan、Cote、Clubb 和 Pishko 以及德克萨斯 A&M 大学的设施将使拟议的研究能够成功完成。该团队利用专业知识来开发拟议的膜和生物传感器，并进行体外和体内分析。