Microneedle arrays for non-invasive continuous multianalyte sensing in diabetes

描述（由申请人提供）：当前一代连续血糖监测仪（cgm）设计用于经皮植入长达7天，之后换能器由佩戴者更换。尽管目前这些设备在分析优点方面取得了进展，但cgm仍然局限于在相对较短的时间内对单一分析物（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。血液儿茶酚胺和酮类是神经递质和代谢物的一些例子，它们可以增强标准血糖测量，从而提供与患者血糖控制和整体代谢健康有关的额外信息。此外，减少换能器元件更换的频率将进一步简化cgm的操作，并在患者的日常工作中提供更多的自主权。鉴于目前cgm的局限性，我们的团队最近率先开发了一种微创体表贴片，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空心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-透皮流体界面上执行各种生物分析功能，并且不需要复杂的微机电或微流体系统进行流体提取和分析。导电聚合物的新实现为生物识别元件的捕获提供了一种有效的手段，同时也提供了赋予高度的热选择性的能力，从而极大地延长了生物传感器的使用寿命和特异性。此外，氟碳糊的使用减少了氧气

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.