Long-term Luminescence-based Glucose Monitoring

描述(申请人提供)：目前可用的连续血糖传感器不准确，容易出现故障，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)。在这一阶段的SBIR中，我们提出了一种注射器可注射的、组织集成的葡萄糖传感器来缓解异物反应，并能够在体内进行至少3周的准确血糖监测。PROFUSA的长期目标是开发一种可自我校准、可植入的CGM，其最短运行寿命为3个月，较长期目标为12个月，其精度将足够高，从而实现人工胰腺。微小、柔软和多孔的组织集成生物传感器正在开发中，这种传感器可以鼓励毛细血管在传感器的整个横截面内和整个横截面上生长，以实现可靠的传感器功能，从而克服快堆的局限性。原型传感器将通过将发光传感纳米球(葡萄糖反应纳米球和参考纳米球)集成到先前开发的血管形成水凝胶支架中(由PROFUSA和合作者通过目前正在进行的赠款开发)来生产。近红外传感器信号通过皮肤通过微型连续光学询问(COIN)贴片读取器读取，该贴片读取器利用新颖的微光学显著降低背景噪音。第一阶段SBIR的目标是用传感器和读取器原型在体内演示传感器的功能。薄膜贴片读取器将持续和离散地监测血糖，这将改善患者的依从性。这项技术的临床翻译将激励和使糖尿病患者更严格地控制他们的血糖水平，而不必担心低血糖，并将减轻糖尿病疾病对医疗系统的负担。 与公共健康相关：糖尿病是一种毁灭性的、代价高昂的慢性疾病，仅在美国就有近2500万人受到影响，每年的医疗支出高达2000亿美元。在我们的新型传感方法在SBIR第一阶段成功进行概念验证后，PROFUSA准备开发一种可自我校准的植入式连续血糖监测仪(CGM)并将其商业化，该监测仪将受到患者的欢迎，并将使人工胰腺成为可能。采用PROFUSA CGM将激励和使糖尿病患者更严格地控制他们的血糖水平，而不必担心严重的血糖低，并将减轻糖尿病疾病对医疗系统的负担。

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.