Long-Term Non-Enzymatic Glucose Sensors for an Artificial Pancreas

用于人工胰腺的长期非酶葡萄糖传感器

• 批准号: 8633308
• 负责人: Natalie Ann Wisniewski
• 金额: $ 22.5万
• 依托单位: PROFUSA, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8633308
• 关键词: Adoption; Affect; Aging; Antioxidants; Area; Artificial Pancreas; Blood capillaries; Boronic Acids; Cells; Characteristics; Chemistry; Chronic Disease; Clinical; Detection; Development; Devices; Diabetes Mellitus; Dyes; Educational workshop; Electronics; Expenditure; Failure; Family suidae; Fibrosis; Film; Fluorescence; Foreign Bodies; Fright; Glucose; Goals; Hand; Health; Healthcare; Healthcare Systems; Hydrogels; Hydrogen Peroxide; Immune; Immune response; Implant; Inflammation; Injectable; Insulin Infusion Systems; Life; Longevity; Marketing; Methods; Modality; Modeling; Monitor; Nanosphere; Nanotechnology; Nature; Optical Readers; Optics; Oxygen; Performance; Phase; Physiological; Plastics; Platinum; Polymers; Proteins; Pump; Reporter; Research; Signal Transduction; Simulate; Skin; Small Business Innovation Research Grant; Solid; Solutions; Stabilizing Agents; Surface; Syringes; System; Technology; Testing; Time; Tissues; United States National Institutes of Health; Variant; Vertebral column; Water; Work; base; burden of illness; capillary; capsule; catalase; commercial application; cost; design; diabetes management; diabetic patient; glucose monitor; glucose sensor; hard metal; implantable device; improved; in vivo; interstitial; luminescence; minimally invasive; nanoparticle; nanosized; novel; optical sensor; oxidation; porous hydrogel; pre-clinical; prototype; public health relevance; response; scaffold; sensor; skin patch; technological innovation

DESCRIPTION (provided by applicant): Despite years of development, currently available continuous glucose monitors (CGMs) still lack good accuracy and reliability for short-term and particularly, long-term use in diabetes management. While insulin pumps work well, CGM remains the single largest hurdle to closing the loop of an artificial pancreas. The main obstacles to achieving a long-term, accurate CGM are instabilities in the sensing chemistry and the body's immune response against the sensor - specifically the foreign body response (FBR) - leading to biofouling, inflammation, avascular fibrosis and sensing chemistry degradation. Additionally, current CGM systems in the market and under development are either bulky percutaneous probes or implantable devices encased in hard metals or plastics that become surrounded by an avascular tissue capsule over time or are taken up by immune cells (if nano-sized). In this Phase I SBIR, we propose to demonstrate the feasibility of a minimally invasive, long-term, non-enzymatic glucose sensor produced using our novel, tissue-integrating "smart" hydrogels that become part of the tissue they are sensing to overcome the FBR. The near infra-red (NIR) fluorescence of the "smart" hydrogel modulates based on the glucose concentration and is detected non- invasively through the skin. The long-term, vascularizing nature of these hydrogel sensors provides exquisite capillary proximity to more than 1000 times greater sensor surface area compared to traditional electrochemical sensors, thereby overcoming the FBR and enhancing accuracy and longevity of glucose detection. The proposed CGM system contains no implanted electronics or hardware in the body. An external optical reader monitors interstitial glucose transdermally based on changes in the NIR optical signal. The optical reader takes the form of a thin-film micro-optical skin patch or a hand-held wand. PROFUSA's long- term goal is to develop a self-calibrating, injectable, soft hydrogel CGM with a minimum operational life of 3 months and a longer-term goal of 12 months with sufficient accuracy to enable an artificial pancreas. Moreover, because of the platform-nature of this technology, sensing nanospheres specific to other analytes (e.g. oxygen, lactate) can also be incorporated within the hydrogel matrix. PROFUSA's tissue-integrating sensor platform has been demonstrated to be stable in the body for months to years and to provide superior sensing performance compared to solid, non-tissue integrating sensors. The overall focus in this proposal is to extend the longevity of fluorescent sensing chemistry to match the observed longevity of the in vivo hydrogel platform. Multiple nanotechnology-based stabilizing agents will be employed. We will evaluate the glucose sensor performance with and without platinum nanospheres, catalase and other antioxidants over time. The ultimate objective is to achieve stable sensor response over 3 months with a maximum 5% loss in sensitivity over 1 month in accelerated aging conditions and H2O2 exposure. Refinement of fluorescent tissue-intergrating sensors promises to open a whole new sensing modality for diabetes management and health monitoring.

描述(申请人提供)：尽管经过多年的发展，目前可用的连续血糖监测仪(CGM)在短期内，特别是在糖尿病治疗中的长期使用方面，仍然缺乏良好的准确性和可靠性。虽然胰岛素泵运行良好，但CGM仍然是关闭人工胰腺环路的最大障碍。实现长期、准确的CGM的主要障碍是传感化学和人体对传感器的免疫反应--特别是异体反应(FBR)--中的不稳定，导致生物结垢、炎症、血管纤维化和传感化学降解。此外，目前市场上和正在开发的CGM系统要么是笨重的经皮探头，要么是包裹在硬金属或塑料中的可植入设备，随着时间的推移，这些设备会被无血管组织囊包围或被免疫细胞(如果是纳米级)所吸收。在这个第一阶段的SBIR中，我们建议展示一种使用我们新型的组织集成“智能”水凝胶生产的微创、长期、非酶血糖传感器的可行性，这种水凝胶成为他们正在传感的组织的一部分，以克服FBR。这种“SMART”水凝胶的近红外(NIR)荧光根据葡萄糖浓度进行调制，并通过皮肤进行非侵入性检测。与传统的电化学传感器相比，这些水凝胶传感器具有长期的血管化特性，使毛细管接近传感器表面积的1000倍以上，从而克服了快速反应，提高了葡萄糖检测的准确性和寿命。建议的CGM系统在体内不包含植入的电子设备或硬件。外部光学读取器根据近红外光学信号的变化经皮监测间质葡萄糖。光学阅读器采用薄膜微光学皮肤贴片或手持棒的形式。PROFUSA的长期目标是开发一种可自我校准、可注射的柔软水凝胶CGM，其最短使用寿命为3个月，较长期目标为12个月，并具有足够的精确度，能够实现人工胰腺。此外，由于这项技术的平台性，针对其他分析物(例如氧气、乳酸)的传感纳米球也可以被结合到水凝胶基质中。PROFUSA的组织集成传感器平台已被证明在体内几个月到几年内都是稳定的，并提供比固体、非组织集成传感器更优越的传感性能。这项提案的总体重点是延长荧光传感化学的寿命，以与体内水凝胶平台的观察寿命相匹配。将使用多种以纳米技术为基础的稳定剂。随着时间的推移，我们将评估使用和不使用铂纳米球、过氧化氢酶和其他抗氧化剂的葡萄糖传感器的性能。最终目标是在3个月内获得稳定的传感器响应，在加速老化和过氧化氢暴露的情况下，1个月内敏感度最大损失5%。荧光组织集成传感器的改进有望为糖尿病管理和健康监测打开一种全新的传感模式。