MICROFABRICATED CONDUCTIMETRIC GLUCOSE SENSOR

微型导电葡萄糖传感器

• 批准号: 2145032
• 负责人: NORMAN F SHEPPARD
• 金额: $ 12.67万
• 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/2145032
• 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.

这项建议描述了一种微细加工的开发 适合皮下使用的电导式葡萄糖生物传感器 植入。I型糖尿病的管理将得到极大的加强 这种传感器的可用性，这种传感器可能用于急性护理 糖尿病高危患者住院等情况 低血糖，或开发胰岛素给药方案。一个 植入式传感器，可可靠工作六个月 当连接到胰岛素输注系统时，将使 人工胰腺。有证据表明，这样的系统将导致 加强血糖控制，减少长期并发症 由这种疾病引起的。 建议的传感器从根本上不同于现有的传感器，以及 是基于对“葡萄糖--”电导率的测量 灵敏的“水凝胶”。葡萄糖氧化酶，固定化在 聚合物凝胶，催化葡萄糖生成葡萄糖酸。这 导致凝胶的膨胀和伴随的电学变化 凝胶的导电性。微型电极，在硅或硅上形成图案 玻璃“芯片”被用来测量凝胶的导电性。一 所提出的电导传感器的潜在优势是 如果有电活性物种的氧化或还原，应该很少 在电极上。因此，响应不应受到以下因素的影响 对乙酰氨基酚等物质会干扰某些电流 传感器。平面微制造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， 皮下植入约0.5毫米。 这里详述的实验计划将导致开发和在 传感器的活体评估。具体目标包括i)继续 制备“葡萄糖响应型”光刻方法的研究进展 确保厚度和成分均匀度的水凝胶；(2)建模 在葡萄糖敏感水凝胶中的扩散反应以帮助 凝胶组成的优化；(3)渗透性选择性凝胶的研制 聚亚安酯外膜，扩大传感器的工作范围； (4)体外测试，以评估和优化传感器的灵敏度、量程、 选择性和反应时间，以及(V)大鼠的急性皮下试验 在动物模型中识别影响传感器性能的因素 生物环境。