SBIR Phase II: A Miniaturized Raman Optical System for Trending Glucose Levels

这个小型企业创新研究(SBIR)第二阶段项目将制作一种可穿戴式拉曼光学系统的原型，以非侵入性、连续和实时地监测趋势血糖水平。一种不显眼、运行时间长、提供绝对血糖读数且只需最小校准的解决方案被认为是糖尿病患者的“圣杯”。在这种抽吸和默认的每日多次手指测量单次血糖读数之间的巨大差异中，存在着在自我调节和针对患者的护理方面改进的令人难以置信的机会。我们的目标是将拉曼系统微型化到10立方厘米以下，以便能够进行经皮血糖检测。寻求足够的准确性，以便对收集的数据进行分析，使临床医生能够提供比单独的手指数据或从糖化血红蛋白(HbA1c)读数推断的两个月平均血糖水平更好的个性化护理。使用在第一阶段开发的新的光学配置，第二阶段的进一步小型化将使我们的实验室台式系统减少到一个手持平台，其体积小一个数量级，并保持必要的吞吐量和灵敏度来活体检测葡萄糖。第二阶段的工作还将研究困扰几乎所有非侵入性血糖检测光学方法的重复性核心问题。具体地说，它将针对第一阶段探索的基于拉曼的光谱配置，将使用光学和机械技术为系统引入稳定性，以减少环境机械和生理扰动以及干扰的影响，这些干扰会导致错误的读数、偏离校准并使最终用户沮丧。这些技术的测试和验证将在体外进行，使用处理过的皮肤、组织和血液样本来创建模型类似物，以取代动物或人类的经皮测试。这最大限度地减少了最初的监管开销，同时提供了基本的测试数据，以确定检测极限、克服重复性的能力以及在现实世界场景中使用的实用性。最终的第二阶段里程碑是交付一个原型进行演示，该原型能够具有足够的灵敏度，并能够稳定地检测和量化血糖的生理水平，以便为可穿戴和可移动设置做好准备。克服这一关键障碍是推进所有此类经皮检测光学技术的必要步骤，也是吸引潜在客户和投资者继续支持商业化的必要步骤。

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.