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

该小型企业创新研究（SBIR）第二阶段项目将开发一种可穿戴拉曼光学系统原型，以无创、连续和实时地监测血糖水平趋势。 对于糖尿病患者来说，一个不显眼、长时间运行并提供最低校准的绝对葡萄糖读数的解决方案被认为是一个“圣杯”。 在这种抽吸和单次血糖读数的每日多次手指针刺测量的默认方案之间的巨大鸿沟中，存在着改善自我调节和患者特定护理的难以置信的机会。 我们的目标是将一个拉曼系统缩小到小于10立方厘米，以实现经皮葡萄糖检测。 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孤立的手指针刺数据或从糖化血红蛋白（HbA1c）读数推断的两个月平均葡萄糖水平更好的个性化护理。 使用一种新的光学配置开发的第一阶段，在第二阶段的进一步小型化将减少我们的实验室台式系统的手持平台，是一个数量级较小，并保持必要的吞吐量和灵敏度检测葡萄糖离vivo.This第二阶段的努力也将调查的核心问题的可重复性几乎所有的光学方法无创葡萄糖检测。 具体来说，它将解决的拉曼为基础的光谱配置在第一阶段探索。 将采用光学和机械技术将稳定性引入系统，以减轻环境机械和生理扰动和干扰的影响，这些扰动和干扰会导致读数错误、校准失败和最终用户受挫。 这些技术的测试和验证将在体外进行，使用处置的皮肤、组织和血液样本来创建模型类似物，以代替动物或人体经皮测试。 这最大限度地减少了初始监管开销，同时提供了必要的测试数据，以确定检测限，克服重复性的能力，以及在现实世界中使用的实用性。 第二阶段的最终里程碑是提供一个原型用于演示，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，可以为可穿戴和非卧床环境做好准备。 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.