Development of (Non) Invasive Real-Time Glucose Sensors

在这个修订后的竞争性更新中，我们建议结合匹兹堡大学化学家和匹兹堡大学医学院医生的专业知识，进一步开发基于智能聚合晶体胶体阵列（IPCCA）化学传感器材料的独特葡萄糖传感材料。糖尿病控制和并发症试验清楚地表明，血糖控制对糖尿病患者至关重要。这需要准确和频繁的血糖监测。然而，目前的家用血糖仪只能精确到15%，需要用手指棒采集血液，而且必须作为单独的工具包随身携带。目前的侵入性方法往往表现出患者依从性差，这对相当大比例的糖尿病患者造成了负面的健康后果。我们的IPCCA材料利用聚合胶体阵列（PCCA），其中含有葡萄糖的识别剂。PCCA包含一个立方阵列的胶体颗粒聚合在水凝胶中。这种PCCA衍射波长由阵列间距决定的光。暴露在葡萄糖中会改变水凝胶的体积，从而改变阵列间距，从而改变衍射波长。在我们探索性资助的工作中，我们对IPCCA葡萄糖传感有了重要的基本理解。我们将开发IPCCA隐形眼镜插入片来检测泪液中的葡萄糖水平，这已经被证明可以跟踪血液中的葡萄糖水平。患者将戴上含有一小块不显眼的IPCCA材料的隐形眼镜，并使用镜子检测镜片插入的颜色，并将其与颜色表进行比较，以确定血糖浓度。此外，我们的研究计划将开发这些用于皮下植入的IPCCA传感器。将IPCCA植入皮下，患者可通过观察其衍射颜色连续监测血糖浓度。工作内容包括：1)ipcc感知机制的基础研究；2)基于IPCCA材料的新型传感元件的开发；3)优化体内使用的传感响应；4)这些装置在正常和四氧嘧啶糖尿病家兔的皮下和眼外葡萄糖检测中的应用。

In this revised competing renewal, we propose to combine the expertise of chemists at the University of Pittsburgh and physicians at the University of Pittsburgh Medical School to further develop our unique glucose sensing materials based on Intelligent Polymerized Crystalline Colloidal Array (IPCCA) chemical sensor materials. The Diabetes Control and Complications Trial clearly demonstrated that glycemic control in patients with diabetes mellitus is crucial. This requires accurate and frequent blood glucose monitoring. However, current home glucose meters are only accurate to 15 percent, require a fingerstick for blood sampling, and must be carried as a separate kit everywhere with the patient. The present invasive methodologies often show poor patient compliance, which translates to negative health consequences for a significant proportion of patients with diabetes mellitus. Our IPCCA materials utilize a polymerized colloidal array (PCCA), which contains a recognition agent for glucose. The PCCA contains a cubic array of colloidal particles polymerized in a hydrogel. This PCCA diffracts light of a wavelength determined by the array spacing. Exposure to glucose changes the hydrogel volume, which changes the array spacing, which alters the diffracted wavelength. We developed important basic understandings of IPCCA glucose sensing in the work performed during our exploratory grant. We will develop IPCCA contact lens inserts to sense the glucose level in the tear fluid, which has been shown to track the glucose level in blood. The patient would wear a contact lens containing a small, unobtrusive section of IPCCA material, and would use a mirror to detect the lens insert color which would be compared to a color chart in order to define the blood glucose concentration. In addition, our research program will develop these IPCCA sensors for use as subcutaneous implants. The IPCCA would be implanted under the skin and the patient could continuously monitor the blood glucose concentration by observing the diffracted color. The work will involve: 1) fundamental studies of the sensing mechanisms of the IPCCA; 2) development of new sensing motifs based on the IPCCA materials; 3) optimization of the sensing response for in vivo use; 4) demonstrations of the utility of these devices for both subcutaneous and extraocular glucose sensing in normal and alloxan diabetic rabbits.