Microneedle arrays for non-invasive continuous multianalyte sensing in diabetes

描述（由申请人提供）：当前一代动态葡萄糖监测仪（CGM）设计为经皮植入长达7天，之后佩戴者更换传感器。尽管这些设备的分析优点的当前进展，CGMs仍然限于在相对短的时间段内的单一分析物（葡萄糖）的定量。然而，人们越来越认识到，适当的血糖管理需要更全面的代谢功能检查。血液中的儿茶酚胺和酮是神经递质和代谢物的一些例子，可以增加标准血糖测量，从而提供有关患者血糖控制和整体代谢健康的额外信息。此外，换能器元件被替换的频率的降低将进一步简化CGM的操作并且在患者的日常生活中提供增加的自主性。鉴于目前CGMs的局限性，我们的团队最近率先开发了一种微创的身体佩戴贴片，该贴片包含具有多路传感元件的可寻址微针阵列。由于电化学换能器嵌入中空微针阵列的孔内的新方法，体上生物传感器能够直接在微针-透皮流体界面处执行各种生物分析功能，并且不需要用于流体提取和分析的复杂的微机电或微流体系统。导电聚合物的新的实施方式提供了用于捕获生物识别元件的有效手段以及赋予高度的选择透过性的能力，从而显著地延长了生物传感器的有用寿命和特异性。此外，碳氟化合物糊剂的使用减轻了氧的氧化。 这种依赖性混淆了当前CGM解决方案中准确的血糖读数。根据项目计划，研究工作旨在实现以下目标：（1） 多分析物微针阵列传感器平台的设计和制造，（2）表面固定和表面化学，以及（3）系统性能的关键评估。拟议的第一阶段研究旨在将微针阵列概念扩展到初步临床研究阶段，以便将这种实验室证明的技术转化为商业产品，可以作为170亿美元全球葡萄糖监测设备和人工胰腺系统市场的主要竞争者。本提案中概述的技术和业务目标将对基础研究和临床应用产生直接影响，以加强血糖管理的现状，从而改善糖尿病患者的健康状况。

DESCRIPTION (provided by applicant): The current generation of continuous glucose monitors (CGMs) are designed to be implanted transdermally for up to seven days after which the transducer is replaced by the wearer. Despite current advances in the analytical merits of these devices, CGMs are still limited to the quantification of a single analyte (glucose) over relatively short periods of time. However, it is increasingly recognized that proper glycemic management requires a more comprehensive examination of metabolic function. Blood catecholamines and ketones are some examples of neurotransmitters and metabolites that can augment standard blood glucose measurements, hence providing added dimensions of information pertaining to the patient's glycemic control and overall metabolic health. Moreover, a reduction in the frequency that the transducer element is replaced would further simplify the operation of CGMs and provide increased autonomy in the patient's routine. In light of the current limitations of CGMs, our team has recently pioneered the development of a minimally-invasive body-worn patch containing an addressable microneedle array with multiplexed sensing elements. Owing to the novel method in which the electrochemical transducer is embedded within the apertures of an array of hollow microneedles, the on-body biosensor is able to perform various bioanalytical functions directly at the microneedle-transdermal fluid interface and does not require sophisticated microelectromechanical or microfluidic systems for fluid extraction and analysis. The novel implementation of conducting polymers provides for both an effective means for the entrapment of the biorecognition element as well as the ability to impart a high degree of perm-selectivity, thereby dramatically extending the biosensor's useful lifetime and specificity. Furthermore, the utilization of a fluorocarbon paste mitigates the oxygen dependency that obfuscates accurate blood glucose readings among current CGM solutions. In accordance with the project plan, the research effort seeks to attain the following objectives: (1) design and fabrication of the multi-analyte microneedle array sensor platform, (2) surface immobilization and surface chemistry, and (3) critical evaluation of the system performance. The proposed Phase I research aims at extending the microneedle array concept up to the stage of preliminary clinical studies in order transform this laboratory-proven technology into a commercial product that can serve as a major contender in the USD $17B global market for glucose monitoring devices and artificial pancreas systems. The technology and business objectives outlined in this proposal will have a direct impact on basic research and clinical applications to enhance the current state of glycemic management and thereby will improve the well-being of the population with diabetes.