Developing a Non-invasive Monitoring System Using NIR Dyes Inside Erythrocytes

描述（由申请人提供）：该合作提案结合了红细胞封装，无创光学监测和光学探针化学合成领域的最新进展，以开发一种新技术，允许长期无创监测关键血液参数。为了实现这种新颖的方法，这是首次尝试将光学传感元件封装在红细胞（红细胞）中以监测血浆参数。结合Meissner小组的生物医学光学知识，Milanick小组的红细胞生理学知识和Glass小组的化学合成能力，将导致一种革命性的无创光学监测技术的展示，可以广泛应用于长期连续监测。将光学传感染料封装在红细胞内，然后将细胞送回动物或人体内，这将首次实现在体内连续数月的无创光学监测。利用生物医学工程、化学和生命科学方面的专业知识，我们合作的目标首先是开发新型近红外荧光传感器，并利用其可逆裂解孔将其加载到红细胞中，其次是开发用于传感器检测的光学仪器，采用综合理论/实验方法，第三是在大鼠模型中测试加载的红细胞和开发的仪器。该项目将导致革命性生物医学传感技术的开发和概念验证，该技术采用功能化红细胞对血液分析物进行长期监测。一种无创血液参数监测系统将对糖尿病等慢性病的疾病/生理跟踪产生重大影响。与传统技术不同的是，这种创新的传感系统利用来自人体的红细胞，这种红细胞可以存活120天，以防止免疫系统的反应。利用红细胞内的光学探针，循环红细胞将提供持续的血液分析样本，并克服传统植入式监测仪的主要障碍。重要的知识和技术装载红细胞与光学主动传感器也将发展。通过光学耦合传感器，该技术可以在很少或没有测量成本的情况下对血液分析物进行无创检测。这有利于按需和连续监测的频繁测试。

DESCRIPTION (provided by applicant): This collaborative proposal combines recent advances in the areas of red blood cell encapsulation, noninvasive optical monitoring and chemical synthesis of optical probes to develop a new technique that allows long term noninvasive monitoring of key blood parameters. To enable this novel methodology, this is the first attempt to encapsulate optical sensing elements in red blood cells (RBCs) to monitor plasma parameters. Combining the biomedical optics knowledge of the Meissner group, the RBC physiology knowledge of the Milanick group and the chemical synthesis abilities of the Glass group will result in the demonstration of a revolutionary noninvasive optical monitoring technique that can be broadly applied to long term continuous monitoring. Encapsulating optical sensing dyes inside RBCs and then returning the cells to the animal or person will for the first time enable continuous noninvasive optical monitoring for months in vivo. Leveraging expertise in biomedical engineering, chemistry and life sciences, the objectives of our collaboration are first to develop novel NIR fluorescent sensors and load them into RBCs using its reversible lysis pore, second to develop optical instrumentation for sensor interrogation with an integrated theory/experiment approach, third to test the loaded RBC's and the developed instrumentation in a rat model. The project will result in the development and proof-of-concept of a revolutionary biomedical sensing technique that employs functionalized RBCs for long term monitoring of blood analytes. A noninvasive monitoring system for blood parameters would have high impact on disease/physiological tracking for chronic conditions such as diabetes. Unlike conventional techniques, the innovative proposed sensing system utilizes cells from the body, RBCs that live for 120 days, to prevent immune system responses. With optical probes inside RBCs, circulating RBCs will provide constant sampling of blood analytes and overcome the major impediment to conventional implantable monitors. Significant knowledge and techniques about loading RBCs with optically active sensors will also be developed. By optically coupling the sensors, the technique enables noninvasive interrogation of blood analytes at little or no measurement cost. This facilitates frequent testing for both on-demand and continuous monitoring. PUBLIC HEALTH RELEVANCE: In this proposal we will develop a novel system for monitoring blood analytes, such as glucose, without the need to draw blood for measurements. The method involves encapsulating fluorescent sensors in red blood cells and making measurement on the sensors through the skin using a simple optical instrument. Once the sensors are in the blood, this method will enable patients and clinicians to perform long-term monitoring of key, blood-born analytes using a noninvasive optical measurement technique.