Long-term Luminescence-based Glucose Monitoring

长期发光血糖监测

• 批准号: 8739006
• 负责人: Natalie Ann Wisniewski
• 金额: $ 7.01万
• 依托单位: PROFUSA, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8739006
• 关键词: Adoption; Affect; Animals; Artificial Pancreas; Back; Biosensor; Blood Glucose; Blood capillaries; Calibration; Chronic; Chronic Disease; Clinical; Color; Complex; Diabetes Mellitus; Disease; Expenditure; Failure; Family suidae; Film; Foreign Bodies; Fright; Glucose; Goals; Grant; Healthcare; Healthcare Systems; Hydrogels; Hypoglycemia; In Vitro; Individual; Injectable; Lead; Length; Life; Light; Measures; Metric; Modeling; Monitor; Nanosphere; Noise; Optical Readers; Optics; Patients; Phase; Production; Quality of life; Reader; Reading; Signal Transduction; Skin; Small Business Innovation Research Grant; Syringes; System; Technology; Testing; Time; Tissues; Translations; base; burden of illness; capillary; commercial application; compliance behavior; density; design; diabetic patient; experience; glucose monitor; glucose sensor; implanted sensor; improved; in vivo; luminescence; meetings; miniaturize; novel; prototype; response; scaffold; sensor; tool

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.

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。

项目成果

Albuminated Glycoenzymes: Enzyme Stabilization through Orthogonal Attachment of a Single-Layered Protein Shell around a Central Glycoenzyme Core.

白化糖酶：通过围绕中央糖酶核心的单层蛋白质壳的正交附着来稳定酶。

• DOI: 10.1021/acs.bioconjchem.6b00103
• 发表时间: 2016
• 期刊: Bioconjugate chemistry
• 影响因子: 4.7
• 作者: Ritter,DustinW;Newton,JaredM;Roberts,JasonR;McShane,MichaelJ
• 通讯作者: McShane,MichaelJ