Development of (Non) Invasive Real-Time Glucose Sensors

在这次修订的竞争更新中，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)化学传感器材料的我们独特的葡萄糖传感材料。糖尿病控制和并发症试验清楚地表明，糖尿病患者的血糖控制至关重要。这需要准确和频繁的血糖监测。然而，目前的家用血糖仪的准确度只有15%，需要用手指抽血，而且必须作为单独的试剂盒随身携带。目前的侵入性方法往往显示患者依从性差，这对相当大比例的糖尿病患者的健康造成了负面影响。我们的IPCCA材料使用聚合胶体阵列(PCCA)，其中包含对葡萄糖的识别剂。PCCA包含在水凝胶中聚合的胶体颗粒的立方体阵列。该PCCA衍射光的波长由阵列间距确定。接触葡萄糖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。我们在探索性拨款期间开展的工作中，对IPCCA葡萄糖传感有了重要的基本理解。我们将开发IPCCA隐形眼镜插件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血糖水平。患者将佩戴含有IPCCA材料的一小段不显眼的隐形眼镜，并使用镜子检测镜片插入的颜色，并将其与色表进行比较，以确定血糖浓度。此外，我们的研究计划将开发这些IPCCA传感器，用于皮下植入。将IPCCA植入皮下，患者可以通过观察衍射色来连续监测血糖浓度。这项工作将包括：1)IPCCA传感机制的基础研究；2)基于IPCCA材料开发新的传感模体；3)体内使用的传感响应的优化；4)展示这些设备在正常和四氧嘧啶糖尿病兔的皮下和眼外血糖传感中的应用。

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.