Long-term Luminescence-based Glucose Monitoring

描述（由申请人提供）：目前可用的连续葡萄糖传感器不准确且易于失效，使得人工胰腺的目标难以实现。此外，它们的设计对患者不友好，并且需要频繁的用户输入（例如校准）。开发植入式葡萄糖传感器的最大障碍是异物反应（FBR）。在该I期SBIR中，我们提出了一种可注射的组织整合葡萄糖传感器，以减轻异物反应，并在体内进行至少3周的准确葡萄糖监测。PROFUSA的长期目标是开发一种自校准的植入式CGM，其最短使用寿命为3个月，长期目标为12个月，其将足够准确，以实现人工胰腺。正在开发微小的、柔软的和多孔的组织集成生物传感器，其鼓励毛细血管在传感器的整个横截面中生长，以允许可靠的传感器功能，从而克服FBR的限制。原型传感器将通过将发光传感纳米球（葡萄糖响应和参考纳米球）整合到先前开发的血管化水凝胶支架（由PROFUSA和合作者通过目前有效赠款开发）中来生产。近红外传感器信号是通过皮肤读取的微型连续光学干涉（COIN）贴片阅读器，利用新颖的微光学显着降低背景噪声。本阶段I SBIR的目标是使用传感器和读取器原型证明体内传感器功能。薄膜贴片阅读器的进步将连续和离散监测血糖将提高患者的依从性。这项技术的临床转化将激励和使糖尿病患者能够更严格地控制他们的葡萄糖水平，而不必担心低血糖，并将减少糖尿病对医疗保健系统的负担。 公共卫生相关性：糖尿病是一种破坏性和昂贵的慢性疾病，仅在美国就影响近2500万人，每年的医疗保健支出高达2000亿美元。在SBIR第一阶段成功验证了我们的新型传感方法后，PROFUSA准备开发和商业化一种自校准的植入式连续葡萄糖监测仪（CGM），该监测仪将被患者接受，并将实现人工胰腺。PROFUSA CGM的采用将激励并使糖尿病患者能够更严格地控制其血糖水平，而不必担心严重的血糖过低，并将减轻糖尿病对医疗保健系统的负担。

DESCRIPTION (provided by applicant): Currently available continuous glucose sensors are inaccurate and prone to failure, making the goal of an artificial pancreas elusive. Furthermore, their designs are not patient-friendly and they require frequent user input (e.g. calibration). The largest hurdle in developing implantable glucose sensors is the foreign body response (FBR). In this Phase I SBIR, we propose a syringe-injectable, tissue-integrating, glucose sensor to mitigate the foreign body response and enable accurate glucose monitoring for a minimum of 3 weeks in the body. PROFUSA's long- term goal is to develop a self-calibrating, implantable CGM with a minimum operational life of 3 months and a longer-term goal of 12 months that will be sufficiently accurate so as to enable an artificial pancreas. Tiny, soft and porous tissue-integrating biosensors that encourage capillaries to grow in and throughout the entire cross section of the sensor are being developed to allow reliable sensor function and thus overcome limitations of the FBR. Prototype sensors will be produced by integrating luminescent sensing nanospheres (glucose-responsive and reference nanospheres) into previously developed vascularizing hydrogel scaffolds (developed by PROFUSA and collaborators through currently active grants). The near infrared sensor signals are read through the skin with a miniaturized Continuous Optical INterrogation (COIN) patch reader that utilizes novel micro-optics to significantly decrease background noise. The goal of this Phase I SBIR is to demonstrate in vivo sensor functionality with the sensor and reader prototypes. Advancements towards a thin-film patch reader that will continuously and discretely monitor blood glucose will improve patient compliance. Clinical translation of this technology will motivate and enable diabetic patients to more tightly control their glucose levels without fear of hypoglycemia, and will reduce the diabetes disease burden on the healthcare system. PUBLIC HEALTH RELEVANCE: Diabetes is a devastating and costly chronic disease affecting nearly 25 million people in the US alone and amounting to $200B in annual healthcare expenditures. Upon successful proof-of- concept demonstration of our novel sensing approach in this SBIR Phase I, PROFUSA is poised to develop and commercialize a self-calibrating, implantable continuous glucose monitor (CGM) that will be embraced by patients and will enable an artificial pancreas. Adoption of the PROFUSA CGM will motivate and enable diabetic patients to more tightly control their glucose levels without fear of severe glucose lows, and will reduce the diabetes disease burden on the healthcare system.