Microneedle arrays for non-invasive continuous multianalyte sensing in diabetes

描述(申请人提供)：当前一代的连续血糖监测仪(CGM)被设计为经皮植入长达7天，之后佩戴者将更换传感器。尽管目前在这些设备的分析价值方面取得了进展，但CGMS仍然仅限于在相对较短的时间内对单一分析物(葡萄糖)进行定量。然而，越来越多的人认识到，适当的血糖管理需要对代谢功能进行更全面的检查。血儿茶酚胺和酮类是神经递质和代谢物的一些例子，可以增强标准的血糖测量，从而提供与患者的血糖控制和整体代谢健康有关的额外维度的信息。此外，减少换能器元件的更换频率将进一步简化CGMS的操作，并在患者的日常工作中提供更多的自主性。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穿戴贴片，其中包含一个带有多路传感元件的可寻址微针阵列。由于电化学换能器被嵌入到中空微针阵列的孔内的新方法，体内生物传感器能够直接在微针-透皮液界面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。导电聚合物的新颖实现为生物识别元件的包埋提供了一种有效的手段，并提供了高度的渗透选择性，从而显著延长了生物传感器的使用寿命和专属性。此外，使用氟碳糊状物可以减少氧气 在当前的CGM解决方案中混淆准确的血糖读数的依赖性。根据项目计划，研究工作力求实现以下目标：(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，以便将这项经过实验室验证的技术转化为商业产品，在价值170亿美元的全球血糖监测设备和人工胰腺系统市场上成为主要竞争者。该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，以改善目前的血糖管理状况，从而改善糖尿病患者的福祉。

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.