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.