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

这个小企业创新研究（SBIR）二期项目将设计一个可穿戴拉曼光学系统的原型，用于无创、连续、实时地监测血糖水平趋势。对于糖尿病患者来说，一种不引人注目、长期运行、只需最少校准即可提供绝对血糖读数的解决方案被认为是“圣杯”。在这种渴望和每天用手指多次测量一次血糖读数的默认方案之间的巨大差异中，存在着改善自我调节和患者特异性护理的难以置信的机会。我们的目标是将拉曼系统缩小到小于10立方厘米，以实现经皮葡萄糖检测。与孤立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相比，需要足够的准确性，以便临床医生能够提供更好的个性化护理。使用第一阶段开发的新型光学结构，第二阶段的进一步小型化将把我们的实验室台式系统缩小到一个手持平台，这是一个更小的数量级，并保持必要的吞吐量和灵敏度来检测体外葡萄糖。第二阶段的工作还将研究困扰几乎所有无创葡萄糖检测光学方法的重复性核心问题。具体来说，将在第一阶段探索的基于拉曼的光谱配置中解决这个问题。光学和机械技术将被用于引入系统的稳定性，以减轻环境机械和生理扰动和干扰的影响，这些干扰会导致错误的读数，偏离校准，并使最终用户感到沮丧。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，以代替动物或人体经皮测试。这可以最大限度地减少初始管理开销，同时提供必要的测试数据，以确定检测限制，克服可重复性的能力，以及在实际场景中使用的实用性。第二阶段的最后一个里程碑是提供一个具有足够灵敏度和稳定的生理血糖水平检测和定量的演示原型，可以用于可穿戴和动态环境。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.