A Hybrid Continuous Glucose and Lactate Monitor with Improved Signal Reliability

“一种信号可靠性更高的混合式连续血糖和乳酸监测仪” Biolinq Inc.(F/K/a Electrzyme LLC) 7.项目总结 在过去的十年里，糖尿病社区从成功的商业化中受益匪浅 多代连续血糖监测仪(CGM)。这些设备能够报告 间质液体(ISF)中的葡萄糖近乎实时地向用户提供。在过去的几年里，主要由 胰岛素依赖型糖尿病患者对改善血糖管理的需求、CGM的准确性和可靠性 设备的进一步进步导致FDA批准使用它们来确定胰岛素剂量而不需要 需要确认性的手指头。最新一代的CGM设备通常用于提供输入到 自动胰岛素输送(AID)系统。然而，尽管CGM技术有这些令人印象深刻的改进， 今天的CGM仍然局限于对单一分析物的测量，并且缺乏获取冗余的能力 测量。人们越来越认识到，在血糖管理方面的进一步进展可能需要 添加其他循环生物标记物来阐明血糖反应的个体变异性，尤其是对 体力活动。自由循环乳酸的测量可以增加已建立的血糖测量，如 已发现乳酸盐可使T1D患者的低血糖阈值降低至较低的血浆水平 葡萄糖浓度[33]。本项目旨在提供一种新型的CGM平台，能够准确地 同时测量葡萄糖和乳酸。我们认为联合监测血糖和乳酸 该系统将增强下一代AID系统的安全性和有效性。Biolinq已经开发出一种 人体佩戴的贴片，包含带有多路传感元件的微针阵列。到目前为止的临床研究已经 使用由插入网状真皮中的可单独寻址的微针组成的微针阵列 -皮肤表面以下约200至350微米。先前的研究表明， 真皮间质液体中的葡萄糖与血糖的相关性[57]。我们的临床研究已经 确认了报告的高水平相关性和先前建立的皮肤中葡萄糖的低滞后时间 ISF[36]；我们认为这是真皮感知的独特特性，可以推广到其他代谢物。 根据项目计划，研究工作力求实现以下目标：(1)发展 乳酸盐选择性传感化学的改进及其与Biolinq‘s的临床验证 葡萄糖选择化学，(2)在微针中实现葡萄糖和乳酸的多余测量 具有可单独寻址的传感元件的阵列传感器平台，可提供准确可靠的 皮肤ISF的测量，以及(3)端到端人体穿戴传感系统的设计，该系统包含 具有蓝牙无线功能的小型化、低功耗专用集成电路。技术 该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 应满足当前对准确、非侵入性的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、简单的使用轮廓和低成本性质，具有广泛的适用性。

"A hybrid continuous glucose and lactate monitor with improved signal reliability" Biolinq Inc. (f/k/a Electrozyme LLC) 7. 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.