Small wearable biosensor patch for continuous and painless alcohol monitoring

小型可穿戴生物传感器贴片，用于连续、无痛酒精监测

• 批准号: 8000603
• 负责人: Joseph marcanio
• 金额: $ 6.17万
• 依托单位: FLEXIBLE MEDICAL SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-05 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8000603
• 关键词: Alcohols; Biosensor; Cells; Chemicals; Chemistry; Communication; Contusions; Detection; Development; Devices; Diabetes Mellitus; Diffusion; Electricity; Electrodes; Employee; Ensure; Glucose; Goals; Heating; In Vitro; Intercellular Fluid; Length; Life; Measurement; Measures; Monitor; Pain-Free; Painless; Patients; Pharmaceutical Preparations; Printing; Process; Reaction Time; Sampling; Sensitivity and Specificity; Skin; Solutions; Stratum corneum; Technology; Testing; Time; Wireless Technology; Work; alcohol measurement; alcohol monitoring; alcohol oxidase; alcohol response; arm; base; cost; flexibility; glucose monitor; glucose oxidase; glucose sensor; human study; human subject; in vitro testing; irritation; microchip; minimally invasive; novel; public health relevance; sensor; sobriety; social; teacher; trend

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.

描述（由申请人提供）：这项工作的总体目标是生产一种无疼痛和无创的可穿戴连续酒精监测器，具有无线通信能力以实现远程监测。该监测器围绕一种新型生物传感器，该生物传感器由多孔柔性微芯片组成，该微芯片破坏死皮细胞的外层，角质层（SC），以进入组织间液（ISF）。该芯片的当前版本正在开发中，用于监测糖尿病患者的葡萄糖，这些版本用于证明核心技术。该装置被证明可以无痛地从人类受试者的手臂上采集ISF，并在体外以高灵敏度和特异性检测葡萄糖。该设备目前正在沃尔特里德陆军糖尿病中心准备进行人体研究。 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醇氧化酶，这与葡萄糖传感器（基于葡萄糖氧化酶）上使用的技术非常相似。我们将依靠我们在生产传感器方面的专业知识，确保酒精监测仪可靠地检测体内的酒精。此外，该技术平台的优势在于，它可以支持额外的化学物质来监测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调整现有的葡萄糖传感器用于酒精监测并在体外测试其功能。该项目的具体目标是：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来创建。检测方法将首先通过在宏电极上涂覆并表征对酒精的响应来验证。如果需要，将在宏电极上进行检测化学的变更。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。将在体外试验中确定灵敏度、特异性、响应时间和测量寿命。 公共卫生相关性FMS设备的几个功能代表了SCRAM和其他酒精监测仪在酒精监测方面的重大进步：7采样过程是无痛和自动的，这将大大提高依从性。7检测组件使用的化学物质与已经使用的化学物质相似，可在ISF中提供准确的葡萄糖测量。7该设备允许频繁、近乎连续地监测酒精水平，这对于趋势分析很重要，可以加强测量的有效性。7可穿戴贴片的超薄外形可实现谨慎的监测。7柔性印刷电路可以廉价地制造，每个芯片上有几十个样品威尔斯。这延长了磨损长度并降低了最终用户成本。7采样过程是微创的（没有任何东西插入皮肤），只定期施加热量和电力，并依赖于被动扩散。将有更少的长期并发症，如刺激和瘀伤，已导致佩戴紧急停堆监视器。7 ISF采样方法应提供比透皮酒精监测更直接的BAC测量方法，其时间滞后更少。FMS设备为其他潜在应用提供了一个平台，这些应用可以从更容易的监测中受益，包括社交饮酒者的清醒度测试;飞行员，教师和其他员工的酒精监测;以及其他物质的测试。