MICROFABRICATED CONDUCTIMETRIC GLUCOSE SENSOR

微型导电葡萄糖传感器

• 批准号: 2145033
• 负责人: NORMAN F SHEPPARD
• 金额: $ 13.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145033
• 关键词: acidity /alkalinity; biomedical equipment development; biosensor device; blood glucose; diffusion; electrical conductance; enzyme activity; evaluation /testing; gel; glass; glucose oxidase; immobilized enzymes; implant; laboratory rat; microelectrodes; molecular film; polymerization; polymers; polyurethanes; silicon

This proposal describes the development of a microfabricated conductimetric glucose biosensor of a size suitable for subcutaneous implantation. Management of Type I diabetes would be greatly enhanced by the availability of such a sensor, which might be used in acute care situations such as hospitalization of a diabetic patient at risk for hypoglycemia, or in developing a insulin administration regimen. An implantable sensor which could operate reliably for a period of six months would, when linked to an insulin infusion system, make feasible an artificial pancreas. There is evidence that such a system would lead to tighter control of blood glucose and reduce the long term complications resulting from the disease. The proposed sensor is fundamentally different from existing sensors, and is based on a measurement of the electrical conductivity of a "glucose- sensitive" hydrogel. The enzyme glucose oxidase, immobilized within a polymer gel, catalyzes the formation of gluconic acid from glucose. This causes swelling of the gel and a concomitant change in the electrical conductivity of the gel. Miniature electrodes, patterned on a silicon or glass "chip" are used to measure the conductivity of the gel. One potential advantage of the proposed conductimetric sensor is that there should be little, if any oxidation or reduction of electroactive species at the electrodes. The response should therefore not be affected by substances such as acetaminophen which can interfere with some current sensors. Planar microfabrication technology simplifies sensor construction and can produce large numbers of identical sensors of the required size, on the order of 0.5 mm for subcutaneous implantation. The experimental plan detailed herein will lead to the development and in vivo evaluation of the sensor. Specific aims include the i) continued development of lithographic methods for preparing "glucose-responsive" hydrogels to insure thickness and compostional uniformity; (ii) modelling of diffusion-reaction in the glucose-sensitive hydrogel to aid in the optimization of the gel composition; (iii) development of permselective polyurethane outer membranes to extend the operating range of the sensor; (iv) in vitro testing to evaluate and optimize sensor sensitivity, range, selectivity and response time, and (v) acute subcutaneous testing in a rat animal model to identify the factors impacting sensor performance in a biological environment.

该建议描述了一种微加工的 电导葡萄糖生物传感器，其尺寸适合于皮下 置入I型糖尿病的管理将大大加强， 这种传感器的可用性，它可以用于急性护理 例如处于糖尿病风险的糖尿病患者的住院治疗的情况 低血糖症，或开发胰岛素给药方案。一个 可植入传感器，可可靠运行6个月 当连接到胰岛素输注系统时， 人工胰腺有证据表明，这样的制度会导致 严格控制血糖，减少长期并发症 由疾病引起的。 所提出的传感器与现有的传感器根本不同， 是基于对"葡萄糖"的电导率的测量， 敏感的"水凝胶。葡萄糖氧化酶，固定在一个 聚合物凝胶，催化葡萄糖形成葡萄糖酸。这 导致凝胶膨胀并伴随着电气变化 凝胶的电导率。微型电极，在硅或 玻璃"芯片"用于测量凝胶的电导率。 一 所提出的电导传感器的潜在优点在于 如果电活性物质有任何氧化或还原， 在电极上。因此，应对措施不应受到 对乙酰氨基酚之类的物质， 传感器.平面微加工技术简化了传感器结构 并且可以生产大量所需尺寸的相同传感器， 对于皮下植入大约为0.5mm。 本文详细介绍的实验计划将导致开发和 传感器的体内评价。具体目标包括：i）继续 用于制备"葡萄糖响应"的光刻方法的发展 水凝胶，确保厚度和成分均匀性;（ii）建模 葡萄糖敏感性水凝胶中的扩散反应，以帮助 优化凝胶组合物;（iii）开发选择性渗透 聚氨酯外膜，以扩展传感器的操作范围; (iv)体外测试以评估和优化传感器灵敏度、范围 选择性和响应时间，以及（v）大鼠中的急性皮下试验 动物模型，以确定影响传感器性能的因素， 生物环境