Development of (Non) Invasive Real-Time Glucose Sensors

在本次修订后的竞争性更新中，我们提议将匹兹堡大学化学家和匹兹堡大学医学院医生的专业知识联合收割机结合起来，进一步开发我们独特的基于智能聚合晶体胶体阵列（IPCCA）化学传感器材料的葡萄糖传感材料。 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，目前的家用血糖仪仅精确到15%，需要手指针刺进行血液采样，并且必须作为单独的套件与患者一起携带。 目前的侵入性方法通常显示出较差的患者依从性，这转化为对相当大比例的糖尿病患者的负面健康后果。我们的IPCCA材料利用聚合胶体阵列（PCCA），其中含有葡萄糖识别剂。 PCCA含有在水凝胶中聚合的胶体颗粒的立方体阵列。 该PCCA衍射由阵列间距确定的波长的光。 暴露于葡萄糖改变了水凝胶体积，这改变了阵列间距，从而改变了衍射波长。 在我们的探索性资助期间进行的工作中，我们对IPCCA葡萄糖传感有了重要的基本理解。我们将开发IPCCA接触透镜插入物来感测泪液中的葡萄糖水平，其已被证明跟踪血液中的葡萄糖水平。 患者将佩戴包含小的、不显眼的IPCCA材料部分的接触透镜，并且将使用镜子来检测透镜插入物的颜色，该颜色将与颜色图表进行比较，以便定义血糖浓度。 此外，我们的研究计划将开发这些IPCCA传感器，用作皮下植入物。 IPCCA将植入皮下，患者可以通过观察衍射颜色连续监测血糖浓度。这项工作将涉及：1）IPCCA传感机制的基础研究; 2）基于IPCCA材料的新传感基序的开发; 3）用于体内使用的传感响应的优化; 4）这些装置用于正常和四氧嘧啶糖尿病兔的皮下和眼外葡萄糖传感的实用性的证明。

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.