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: 8554303
• 负责人: Melissa Grunlan
• 金额: $ 29.6万
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8554303
• 关键词: Affect; Alexa594; Binding Sites; Biological Assay; Biosensor; Blood Glucose; Caliber; Cells; Chronic Disease; Collaborations; Concanavalin A; Coupled; Detection; Development; Devices; Diabetes Mellitus; Diffuse; Diffusion; Dimensions; Elements; Excision; Exhibits; Failure; Fingers; Fluorescence; Frequencies; Funding; Glucose; Goals; Health; Heating; Housing; Hydrogels; Immune response; Implant; In Vitro; Injection of therapeutic agent; International; Legal patent; 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; functional restoration; glucose monitor; implantation; implanted sensor; improved; in vivo; innovation; monitoring device; multidisciplinary; nanocomposite; nanoparticle; novel strategies; poly-N-isopropylacrylamide; programs; sensor; subcutaneous; Affect; Alexa594; Binding Sites; Biological Assay; Biosensor; Blood Glucose; Caliber; Cells; Chronic Disease; Collaborations; Concanavalin A; Coupled; Detection; Development; Devices; Diabetes Mellitus; Diffuse; Diffusion; Dimensions; Elements; Excision; Exhibits; Failure; Fingers; Fluorescence; Frequencies; Funding; Glucose; Goals; Health; Heating; Housing; Hydrogels; Immune response; Implant; In Vitro; Injection of therapeutic agent; International; Legal patent; 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; functional restoration; glucose monitor; implantation; implanted sensor; 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）：糖尿病是国际健康问题，全球数百万患者。开发一种生物传感器技术是一种未满足的需求，该技术是一种快速，方便的方法，可以不断监测糖尿病患者的血糖水平。拟议的工作旨在开发可植入的葡萄糖生物传感器，该生物传感器可以在长时间内监测葡萄糖水平（3-6个月）。与现有的连续葡萄糖监测装置（令人失望的寿命为3-7天）相比，拟议的植入葡萄糖生物传感器设计截然不同，预计将提高长期疗效。提出的植入式葡萄糖生物传感器的创新方面包括：（1）一种自我清洁的膜，（2）一种荧光葡萄糖传感测定法，其中包含在膜上形成生物传感器的荧光葡萄糖传感测定，（3）（3）终端的生物传感器设计，可通过良性皮下监测和便利的Glucose Glucose Glucose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。提出的“自我清洁”膜在控制生物污染的方法上是不同的。它旨在显示出积极的“自我清洁”，这是由于其热响应性质。该膜将基于热纳米复合材料水凝胶，该水凝胶通过外部加热源热循环。该膜将用于容纳葡萄糖传感测定法，该测定法显示出具有更大的生理葡萄糖水平动态范围，而其他光学荧光葡萄糖感应方法则具有更大的动态范围。最后，将组合膜和传感测定法，形成具有圆柱几何形状（预期尺寸<5 mm直径<5 mm，长度<10 mm）的生物传感器，这允许方便植入，更换和患者葡萄糖监测的最终使用设计。最终，在注射到腕部的皮下组织后，戴在植入的生物传感器位置上的手表装置将包含用于非侵入性连续葡萄糖传感的光学探针，以及用于膜清洁的热加热元件（即热循环）。 DRS的多学科团队。 Grunlan，Cote，Clubb和Pishko以及德克萨斯A＆M大学的设施将成功完成拟议的研究。该团队带来了开发拟议的膜和生物传感器的专业知识，并进行体外和体内分析。