SBIR-STTR Award

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

This Small Business Innovation Research (SBIR) Phase II project shall prototype a wearable Raman optical system to monitor trending blood glucose levels noninvasively, continuously, and in real-time. A solution that is unobtrusive, long-running, and provides absolute glucose readings with minimal calibration is considered a "holy grail" for patients with diabetes mellitus. In the vast divide between this aspiration and the default regimen of multiple daily fingerstick measurements for single-shot glucose readings lie incredible opportunities for improvement in self-regulation and patient-specific care. Our goal is to miniaturize a Raman system into less than 10 cubic centimeters to enable transcutaneous glucose detection. Sufficient accuracy is sought so that analysis of collected data allows clinicians to provide better individualized care than is possible with either isolated fingerstick data or two-month-averaged glucose levels inferred from glycated hemoglobin (HbA1c) readings. Using a novel optical configuration developed in Phase I, further miniaturization in Phase II will reduce our laboratory bench-top system to a handheld platform that is an order of magnitude smaller and maintains the necessary throughput and sensitivity to detect glucose ex vivo.This Phase II effort will also investigate the core problem of repeatability plaguing almost all optical approaches for noninvasive glucose detection. Specifically, it will be addressed for the Raman-based spectroscopic configuration explored in Phase I. Optical as well as mechanical techniques will be employed to introduce stability into the system to mitigate contributions from ambient mechanical and physiological perturbations and disturbances that cause errant readings, throw off calibrations, and frustrate end users. Testing and validation of these techniques will be performed ex vivo, using disposed skin, tissue and blood samples to create model analogues in place of animal or human transcutaneous testing. This minimizes initial regulatory overhead while providing essential test data to ascertain detection limits, capacities for overcoming repeatability, and practicalities for usage in real-world scenarios. The end Phase II milestone is to deliver a prototype for demonstration that is capable of sufficient sensitivity, and stabilized detection and quantification of physiological levels of blood glucose that can be readied for wearable and ambulatory settings. Overcoming this key hurdle is a necessary step to advance all such optical technologies for transcutaneous detection, and one which will engage potential customers and investors for continued support toward commercialization.