A Hybrid Continuous Glucose and Lactate Monitor with Improved Signal Reliability

“具有改进的信号可靠性的混合连续葡萄糖和乳酸监测器” Biolinq公司（f/k/a Electrozyme LLC） 7.项目摘要 在过去的十年里，糖尿病社区从成功的商业化中受益匪浅。 连续血糖监测仪（CGMs）的发展。这些设备能够报告 组织间液（ISF）中的葡萄糖以接近实时的方式提供给用户。在过去的几年里，主要是由 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展，导致FDA批准其用于确定胰岛素剂量，而无需 需要确认指纹最新一代的CGM设备通常用于提供输入， 自动胰岛素输注（AID）系统。然而，尽管CGM技术有了这些令人印象深刻的改进， 今天的CGMs仍然局限于测量单个分析物，并且缺乏采用冗余分析物的能力。 测量.越来越多的人认识到，血糖管理的进一步发展可能需要 增加其他循环生物标志物以阐明血糖反应的个体差异，特别是 体力活动。自由循环乳酸盐的测量可以增加已建立的葡萄糖测量， 已发现乳酸盐可改变T1 D患者低血糖的血糖阈值， 葡萄糖浓度[33]。因此，本项目旨在提供一种新型的CGM平台，能够准确地 测量葡萄糖和乳酸盐。我们认为联合葡萄糖和乳酸盐连续监测 该系统将提高下一代AID系统的安全性和有效性。Biolinq开发了一种 包含具有多路复用传感元件的微针阵列的体戴式贴片。迄今为止的临床研究 使用由插入网状真皮的可单独寻址的微针组成的微针阵列 - 在皮肤表面下约200至350微米处。以前的工作表明， 真皮间质液中葡萄糖与血糖之间的相关性[57]。我们的临床研究 证实了高水平的相关性报告和低滞后时间以前建立的葡萄糖在皮肤 ISF [36];我们认为这是真皮中传感的独特特性，可以扩展到其他代谢物。 根据项目计划，研究工作旨在实现以下目标：（1）开发 乳酸盐选择性传感化学的改进及其与Biolinq临床验证的 葡萄糖选择性化学，（2）在微针中实施葡萄糖和乳酸盐的冗余测量 阵列传感器平台具有可单独寻址的传感元件， 皮肤ISF中的测量，以及（3）包含传感器的端到端身体穿戴感测系统的设计。 小型化、低功耗、具有蓝牙无线功能的专用集成电路。技术 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 并应满足当前对准确、无创连续葡萄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而具有广泛的适用性。

"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.