In Vitro Feasibility of a Rapid Response Continuous Glucose Sensor

描述（由申请人提供）：许多研究出版物已经证明了动态葡萄糖监测的益处，可以更好地控制葡萄糖和降低糖化血红蛋白（HbA 1c）水平;但是，为了提高有效性，需要显著改善植入式葡萄糖探头的性能。拟议的第一阶段研究重点是开发一种快速、微秒、微创的连续葡萄糖监测仪，解决目前市售的连续葡萄糖监测仪（CGMs）的许多局限性，包括：身体的免疫反应（也称为生物污垢）、动态范围、传感器滞后和低血糖范围（<70 mg/dL）的准确性。具体目标包括开发一种新技术，用于测量以前未描述的微秒级酶反应。此外，这项研究将产生一个更好的理解发生在20 E的生物传感器表面的化学和电化学过程。这项研究的结果还将产生人体免疫反应对传感器输出影响的近瞬时指示，从而实现无误差的体内葡萄糖测量，传感器延迟基本为零。这将减少与间质液葡萄糖测量相关的总体滞后时间;从而显著提高准确性。不准确性限制了FDA对CGMs的上市前批准，使其只能用于手指针刺监测的连续治疗。这意味着在调整胰岛素剂量或饮食之前，必须通过手指针刺测量确认CGM的所有读数。从长远来看，为了使连续葡萄糖监测获得更广泛的消费者接受和医疗保险和健康保险公司的报销，需要提高准确性，并减少或消除对CGM传感器定期重新校准的要求。这项拟议的第1阶段研究的成功完成将为连续葡萄糖监测技术提供重大进展，有可能解决用户面临的许多准确性和校准问题。此外，提高准确性和纠正生物污垢的能力将提供医疗保险提供者要求报销的额外疗效数据，并使人工胰腺的概念更接近现实。公共卫生相关性：缺乏持续控制和葡萄糖浓度监测不充分以避免血糖波动给国家医疗保健系统带来了高昂的成本，并对糖尿病和葡萄糖耐量受损患者的疾病进展和继发性并发症产生了明显影响。由于准确性问题和频繁重新校准的需要，目前FDA批准的第一代连续葡萄糖监测（CGM）设备已获得胰岛素依赖型糖尿病患者、监管机构和第三方保险付款人的有限或有条件接受。所提出的CGM系统的微秒采样率和信号处理算法克服了现有的技术限制，并提供了比当前设备高几个数量级的测量和控制分辨率，从而使“闭环”人工胰腺成为近期现实。

DESCRIPTION (provided by applicant): Numerous research publications have demonstrated the benefits of continuous glucose monitoring for better glucose control and reduced glycated hemoglobin (HbA1c) levels; however, to improve efficacy, significant improvements in the performance of implanted glucose sensors are required. The proposed Phase 1 research is focused on developing a rapid, microsecond, minimally invasive, continuous glucose monitor that addresses many of the limitations of currently marketed Continuous Glucose Monitors (CGMs) including: the body's immune response also known as biofouling, dynamic range, sensor lag, and accuracy in the hypoglycemic range (<70 mg/dL). Included in the Specific Aims is the development of a new technology for measuring enzymatic reactions occurring on a microsecond scale that have not been described previously. In addition, this research will yield a better understanding of both chemical and electrochemical processes occurring within 20E of a biosensor surface. The results of this research will also yield a near instantaneous indication of the effects of the body's immune response on the sensor output, thus enabling error free in vivo glucose measurements with essentially zero sensor lag. This will reduce the overall lag-time associated with interstitial fluid glucose measurements; thereby, significantly improving accuracy. Inaccuracy has limited FDA pre-market approval of CGMs to adjunctive therapy to fingerstick monitoring. This means all readings from the CGM must be confirmed by fingerstick measurements prior to adjustments in insulin dosage or diet. In the long-term, for continuous glucose monitoring to gain wider consumer acceptance and reimbursement by Medicare and health Insurers, accuracy needs to be improved and the requirement for periodic re-calibration of CGM sensors reduced or eliminated. Successful completion of this proposed Phase 1 research will provide significant advances in continuous glucose monitoring technology that have the potential to resolve many of the accuracy and calibration issues faced by users. Furthermore, improved accuracy and the ability to correct for biofouling will provide additional efficacy data that health insurance providers are demanding for reimbursement, and bring the concept of the artificial pancreas one step closer to reality. PUBLIC HEALTH RELEVANCE: The lack of sustained control and inadequate monitoring of glucose concentration to avoid glycemic excursions comes at a high cost to the national healthcare system, and has a demonstrated impact on disease progression and secondary complications for patients with diabetes and impaired glucose tolerance. Current 1st generation FDA approved continuous glucose monitoring (CGM) devices have gained limited or conditional acceptance by insulin dependent diabetics, regulatory agencies, and third- party insurance payers due to accuracy problems and the need for frequent recalibration. The micro- second sampling rate and signal processing algorithms of the proposed CGM system overcome existing technical limitations and provide a resolution of measurement and control on a scale orders of magnitude higher than current devices, thereby making the "closed loop" artificial pancreas a near-term reality.