This Small Business Innovation Research Program Phase I project proposes to develop a handheld Raman optical system for monitoring blood glucose levels noninvasively, continuously, and in real-time. Raman spectroscopy uses laser light scattered by chemical species to distinguish, identify, and quantify them based on the shifted spectrum found in their optical fingerprint. The fingerprint of glucose can be used to key in and register its changes in concentration over time in biological tissues, such as in the interstitial fluid and in the blood. The objectives of this project are to miniaturize an existing Raman bench-top system to one that is wearable, low-cost, and optimized for blood glucose measurement in diabetic patients. Because this approach is noninvasive, it has the potential to limit the multiple-daily finger prick measurements required to draw blood for glucose measurement, and obviates biofouling issues associated with existing commercial continuous glucose monitors that require catheter inserts. Because it can measure continuously, measurements can provide curve data instead of static single-shot measurements from each finger prick. Glucose dynamics obtained from this data can then be used to establish a better regimen for glucose control with a combination of better diets and improved insulin dosage. The broader impact/commercial potential of this project is to help improve the lives of 26 million American diabetics where blood glucose control is central to their health. The Center for Disease Control (CDC) predicts one out three Americans (almost 150 million) will be diabetic by 2050. The American Diabetes Association (ADA) and CDC also estimate the existing cost in the United States of diabetes, direct and indirect, to be $108B ~ $174B annually. These costs can be significantly mitigated with better management of care, where accessibility and adoption of newer, cost-effective, easy-to-integrate, and easy-to-use technologies can reduce direct costs, and where preventative warnings could reduce indirect costs. If this program's miniaturization thrust succeeds, there are multiple blood analytes that a handheld platform could address, including ketones, lactates, urea, cholesterol, hematocrit, and alcohol. As an example, law enforcement could use it in the field to detect illegal substances in the bloodstream. Miniaturization also enables mobile self-diagnostics and patient compliance, two enormous emerging markets. The ability to relay diagnostic data to clinicians remotely and in real-time for analysis to portend medical emergencies would be revolutionary