Small wearable biosensor patch for continuous and painless alcohol monitoring

描述（由申请人提供）：这项工作的总体目标是生产一种无痛、无创的可穿戴连续酒精监测仪，具有无线通信能力，可以进行远程监测。该监视器围绕一种新型生物传感器展开，该传感器由一个多孔柔性微芯片组成，可破坏死皮细胞的外层角质层（SC），以获取间质液（ISF）。目前该芯片的版本正在开发中，用于监测糖尿病患者的血糖，这些版本被用来验证核心技术。该装置被证明可以无痛地从人类受试者的手臂上取样ISF，并在体外以高灵敏度和特异性检测葡萄糖。该设备目前正准备在沃尔特里德陆军糖尿病中心进行人体研究。在这项研究中，我们将调整葡萄糖传感器来测量酒精。电化学检测策略利用乙醇氧化酶，这与葡萄糖传感器上使用的技术非常相似（这是基于葡萄糖氧化酶）。我们将依靠我们在生产传感器方面的专业知识，确保酒精监测器可靠地检测体内的酒精。此外，该技术平台的一个优势在于，它可以支持其他化学物质，以监测ISF中可能存在的其他物质，包括酒精以外的药物。本文提出的工作范围是将现有的葡萄糖传感器用于酒精监测，并在体外测试其功能。本项目的具体目标是：1。完成酒精检测化学。酒精检测层最初将使用与葡萄糖监测器相同的策略和化学物质创建。检测方法将首先通过在宏观电极上涂覆并表征对酒精的响应来验证。如果需要，将在宏观电极上改变检测化学。2. 功能化FMS芯片。现有的芯片平台将被功能化，以检测酒精。在宏观电极上给出最佳结果的检测化学将应用于FMS芯片，并在酒精溶液中验证该方法。3. 表征酒精传感器。灵敏度、特异性、反应时间和测量寿命将在体外试验中确定。

DESCRIPTION (provided by applicant): The overall goal of this work is to produce a wearable continuous alcohol monitor that is pain- free and noninvasive, with wireless communications capability to enable remote monitoring. The monitor centers around a novel biosensor consisting of a multi-well flexible microchip that disrupts the outer layer of dead skin cells, the stratum corneum (SC), to access interstitial fluid (ISF). Current versions of the chip are in development to monitor glucose for patients with diabetes and these versions were used to prove the core technology. The device was shown to sample ISF painlessly from the arm of human subjects, and to detect glucose with high sensitivity and specificity in vitro. The device is currently being prepared for a human study at the Walter Reed Army Diabetes Center. In this study we will adapt the glucose sensor to measure alcohol. The electrochemical detection strategy utilizes alcohol oxidase which is very similar to the technology used on the glucose sensor (which was based on glucose oxidase). We will rely on our expertise in producing sensors to ensure the alcohol monitor detects alcohol in the body reliably. Moreover, a strength of the technology platform is that it can support additional chemistries to monitor other substances that may be present in the ISF, including drugs in addition to alcohol. The scope of the work proposed herein is to adapt the existing glucose sensor for alcohol monitoring and test its function in vitro. The specific aims of this project are: 1. Finalize alcohol detection chemistry. The alcohol detection layer will initially be created using the same strategy and chemicals as the glucose monitor. The detection approach will first be verified by coating on a macro electrode and characterizing the response to alcohol. Changes in the detection chemistry, if needed, will be made on the macro electrode. 2. Functionalize FMS chip. The existing chip platform will be functionalized to detect alcohol. The detection chemistry that gave the best results on the macro electrode will be applied to the FMS chip, and the approach verified in alcohol solutions. 3. Characterize alcohol sensor. The sensitivity, specificity, response time, and measurement life will be determined in in vitro tests. PUBLIC HEALTH RELEVANCE Several features of the FMS device represent significant advances for alcohol monitoring over the SCRAM and other alcohol monitors: 7 The sampling process is painless and automatic, which will dramatically increase compliance. 7 The detection component uses chemistries similar to those already in use that provide accurate glucose measurement in ISF. 7 The device allows frequent, near-continuous monitoring of alcohol levels which is important for trending, which can bolster the validity of measurements. 7 The slim profile of a wearable patch enables discreet monitoring. 7 Flexible printed circuits may be manufactured inexpensively with dozens of sample wells on each chip. This extends wear length and lowers end user costs. 7 The sampling process is minimally-invasive (nothing inserts into the skin), only applies heat and electricity periodically, and relies on passive diffusion. There will be fewer long- term complications such as irritation and bruising that have resulted from wearing SCRAM monitors. 7 The ISF sampling approach should provide a more direct measure of BAC with less of a time lag than transdermal alcohol monitoring. 7 The FMS device offers a platform for other potential applications that could benefit from easier monitoring, including sobriety tests for social drinkers; alcohol monitoring for pilots, teachers, and other employees; and testing for other substances.