A Hybrid Continuous Glucose and Lactate Monitor with Improved Signal Reliability

具有更高信号可靠性的混合连续血糖和乳酸监测仪

• 批准号: 10597237
• 负责人: Jared Rylan Tangney
• 金额: $ 78.64万
• 依托单位: BIOLINQ INCORPORATED
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10597237
• 关键词: Apple; Archives; Biosensor; Blood Glucose; Bluetooth; Buffers; Businesses; Characteristics; Chemistry; Clinical; Clinical Research; Communities; Continuous Glucose Monitor; Custom; Data Display; Databases; Dermal; Dermis; Detection; Development; Devices; Diabetes Mellitus; Diameter; Dimensions; Dose; Effectiveness; Elements; Ensure; Evaluation; Fingers; Generations; Glucose; Glucose Plasma Concentration; Height; Hormones; Hour; Hybrids; Hypoglycemia; In Vitro; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; Intercellular Fluid; Lead; Measurement; Measures; Monitor; Nature; Needles; Noise; Oxidases; Pain Free; Patients; Performance; Phase; Phosphate Buffer; Physical activity; Physiologic pulse; Physiological; Property; Reporting; Research; Resolution; Safety; Sampling; Secure; Signal Transduction; Skin; Sterility; Sterilization; Surface; System; Systems Development; Technology; Time; Transducers; Translating; Validation; Work; battery life; biomaterial compatibility; circulating biomarkers; cloud based; commercialization; cost; design; detection limit; diabetes management; improved; individual variation; insight; integrated circuit; miniaturize; mobile application; monitoring device; next generation; novel; parallelization; rate of change; response; sensor; wireless

PROJECT SUMMARY Over the past decade, the diabetes community has benefited enormously from the successful commercialization of multiple generations of continuous glucose monitors (CGMs). These devices are able to report readings of glucose in the interstitial fluid (ISF) to users on a near real-time basis. Over the few years, driven primarily by demands for improved glycemic management in insulin-dependent diabetes, the accuracy and reliability of CGM devices made further advances leading to FDA approval of their use in determining insulin dosing without the need for confirmatory fingersticks. The latest generation of CGM devices are routinely used to provide input to automated insulin delivery (AID) systems. However, despite these impressive improvements in CGM technology, CGMs today remain limited to the measurement of a single analyte and lack the ability to take redundant measurements. It is increasingly recognized that further advances in glycemic management will likely require the addition of other circulating biomarkers to elucidate individual variability in glycemic response, especially to physical activity. Measurement of freely circulating lactate can augment established glucose measurements as lactate has been found to shift glycemic thresholds for hypoglycemia in individuals with T1D to lower plasma glucose concentrations [33]. This project thus aims to provide a novel CGM platform capable of accurately measuring both glucose and lactate. We believe that a combined glucose and lactate continuous monitoring system will enhance the safety and efficacy of the next generation of AID systems. Biolinq has developed a body-worn patch containing a microneedle array with multiplexed sensing elements. Clinical studies to date have used a microneedle array consisting of individually-addressable microneedles inserted into the reticular dermis – approximately 200 to 350 microns below the surface of the skin. Previous work has shown a high level of correlation between glucose in the dermal interstitial fluid and blood glucose [57]. Our clinical studies have confirmed the high level of correlation reported and low lag time previously established for glucose in the dermal ISF [36]; we believe this is a unique property of sensing in the dermis and can be extended to other metabolites. In accordance with the project plan, the research effort seeks to attain the following objectives: (1) development and refinement of a lactate-selective sensing chemistry and its co-location with Biolinq’s clinically-validated glucose-selective chemistry, (2) implementation of redundant measures of glucose and lactate in a microneedle array sensor platform featuring individually-addressable sensing elements to provide accurate and reliable measurements in the dermal ISF, and (3) design of an end-to-end body-worn sensing system containing a miniaturized, low-power application-specific integrated circuit with Bluetooth wireless capability. The technology and business objectives outlined in this proposal will have a direct impact on open- and closed-loop insulin delivery and should meet current needs for an accurate, non-invasive continuous glucose and lactate monitor with broad applicability owing to its enhanced reliability, accuracy, simple use profile, and low-cost nature.

项目概要 在过去的十年中，糖尿病界从成功的商业化中受益匪浅 这些设备能够报告多代连续血糖监测仪 (CGM) 的读数。 近几年来，主要由以下因素推动：间质液 (ISF) 中的葡萄糖近乎实时地提供给用户。 改善胰岛素依赖型糖尿病血糖管理的需求、CGM 的准确性和可靠性 设备取得了进一步的进步，导致 FDA 批准将其用于确定胰岛素剂量，而无需 需要确认指尖刺痛 最新一代的 CGM 设备通常用于提供输入。 然而，尽管 CGM 技术取得了这些令人瞩目的进步， 如今的 CGM 仍然仅限于测量单一分析物，并且缺乏冗余分析的能力 人们越来越认识到，血糖管理可能需要进一步进步。 添加其他循环生物标志物来阐明血糖反应的个体差异，尤其是 体力活动测量自由循环的乳酸可以增强已建立的葡萄糖测量结果。 研究发现乳酸可以改变 T1D 患者发生低血糖的血糖阈值，从而降低血浆水平 因此，该项目旨在提供一种能够准确测量葡萄糖浓度的新型 CGM 平台。 我们认为，葡萄糖和乳酸的联合连续监测。 系统将增强 Biolinq 开发的下一代 AID 系统的安全性和有效性。 迄今为止的临床研究表明，这种贴片含有带有多路传感元件的微针阵列。 使用由可单独寻址的微针组成的微针插入阵列进入网状真皮 – 皮肤表面以下约 200 至 350 微米处，先前的研究显示出高水平。 我们的临床研究发现真皮间质液中的葡萄糖与血糖之间存在相关性[57]。 证实了所报道的高水平相关性和先前建立的真皮中葡萄糖的低滞后时间 ISF [36]；我们相信这是真皮中传感的独特特性，并且可以扩展到其他代谢物。 根据项目计划，研究工作力求达到以下目标：（1）开发 乳酸选择性传感化学的改进及其与 Biolinq 经临床验证的共定位 葡萄糖选择性化学，(2) 在微针中实施葡萄糖和乳酸的冗余测量 阵列传感器平台具有可单独寻址的传感元件，可提供准确可靠的 真皮 ISF 中的测量，以及 (3) 端到端身体佩戴传感系统的设计，其中包含 具有蓝牙无线功能的小型化、低功耗专用集成电路。 本提案中概述的业务目标将对开环和闭环胰岛素产生直接影响 交付并应满足当前对准确、无创连续血糖和乳酸监测仪的需求 由于其增强的可靠性、准确性、简单的使用配置和低成本，因此具有广泛的适用性。