InstaCortisol:A realtime and continuous assessment of Cortisol in ISF

描述(由申请人提供)：“StressSmart”反复暴露在心理社会压力下与几种人类疾病(如癌症、药物成瘾、心脏病、抑郁症)有关，造成巨大的公共卫生负担。然而，我们的进展受到限制，因为缺乏一种便携式设备，能够像个人在自然环境中所经历的那样，实时、可靠、非侵入性地连续测量个人暴露在心理社会压力下的情况。在这个跨学科的项目中，我们建议开发一种名为InstaCortisol(Tm)的新测试，该测试可以通过测量受试者在自然环境中的皮质醇水平，用于可靠、选择性和快速地量化个人压力暴露。皮质醇是肾上腺皮质产生和分泌的主要类固醇，被用作压力的可靠指标。这种快速检测方法基于免疫电化学法，当皮质醇夹在捕获抗体和附着在碱性磷酸酶上的检测器抗体之间时，反应信号通过循环伏安法测量。这个项目有四个具体目标。首先是传感器制造：我们将在前两个月制造多个皮质醇传感器。第二是传感器评估：我们将测试传感器的灵敏度、特异性、酶/抗体稳定性、检测限、线性、准确度、动态范围、重复性、精密度、准确度、干扰、交叉反应、漂移和传感器校准。我们预计将改变和/或优化制造方法，以实现这些类别中的每一项基准。第三是传感器性能：确定传感器性能与商用皮质醇传感器的性能。考虑到对现成的皮质醇传感器的持续性能基准的需求，我们的目标是达到或超过。第四，将设计集成可行性实验：对皮质醇传感器芯片进行虚拟评估，并将其集成成紧凑、易用的设计。相关性：InstaCortisol(Tm)测试(在第一阶段开发)将在第二阶段成为StressSmart(Tm)设备的一部分，它将使研究人员能够量化个人在现实生活中经历的心理社会压力。这种能力将增进我们对心理社会压力暴露如何与人类流行疾病的遗传因素相互作用的理解，这些疾病给公共卫生造成了巨大的负担。与公共健康相关：我们建议进行皮质醇的快速检测，称为“InstaCortisol”，它将通过检测间质液体中的皮质醇(ISF)，对个人暴露于心理社会应激中进行实时和连续的定量、选择性、客观、可靠和安全的测量。ISF将使用我们专有的名为“LightAccess”的微创设备进行采集。拟议的产品涉及几项尖端技术的整合。该产品几乎不需要受试者或患者采取任何行动，从而大大减少了与不当使用相关的错误。这些创新将为评估在许多生物过程和疾病状态中发挥重要作用的分子提供一种显著改进的方法。

DESCRIPTION (provided by applicant): "StressSmart" Repeated exposures to psychosocial stress are associated with several human diseases (e.g., cancer, drug addiction, heart disease, depression) of tremendous public health burden. However, our progress is limited by the lack of a portable device that can enable rapid, reliable, non-invasive and continuous measurement of personal exposure to psychosocial stress in real-time, as experienced by individuals in their natural environments. In this interdisciplinary project, we propose to develop a new test called InstaCortisol(tm) that can be used to reliably, selectively and rapidly quantify personal exposures to stress by measuring Cortisol levels of subjects in their natural environments. Cortisol is the primary steroid produced and secreted by the adrenal cortex and is used as a reliable indicator of stress. This rapid test is based on immunoelectrochemical method where the reaction signal is measured by using cyclic voltammetry, when Cortisol sandwiches between the capture and the detector antibody, which is attached to Alkaline Phosphatase enzyme. There are four specific aims of this project. First is Sensor Fabrication: We will fabricate multiple Cortisol sensors in first two months. Second is Sensor Evaluation: we will test the sensors for sensitivity, specificity, enzyme/antibody stability, detection limit, linearity, accuracy, dynamic range, repeatability, precision, accuracy, interference, cross-reactivity, drift, and sensor calibration. We anticipate changing and/or optimizing fabrication methods to achieve benchmarks in each of these categories. Third is sensor performance: Establish sensor performance against commercially available Cortisol sensors. We aim to meet or exceed, given the need for continuous performance benchmarks of readily available Cortisol sensors. Fourth would be to Design integration feasibility experiments: A virtual evaluation of Cortisol sensor chip and its integration into a compact easy to use design. Relevance: The InstaCortisol(tm) test (being developed during Phase I), which will be part of StressSmart(tm) device during Phase II, will enable researchers to quantify personal exposure to psychosocial stress, as experienced by individuals in real-life situations. Such a capability will advance our understanding of how exposures to psychosocial stress interact with genetic factors in the etiology of prevalent human diseases of tremendous public health burden. PUBLIC HEALTH RELEVANCE: We are proposing to make a rapid test for detecting Cortisol, called "InstaCortisol", which will make real-time and continuous measurements of personal exposure to psychosocial stress quantitatively, selectively, objectively, reliably, and securely by detecting Cortisol in interstitial fluid (ISF). ISF will be harvested using our proprietary minimally invasive device called "LightAccess". The proposed product involves the integration of several cutting edge technologies. The product would require virtually no action on the part of the subject or patient thereby greatly reducing error associated with improper use. These innovations would provide a significantly improved method for assessing a molecule that plays an important role in many biological processes and disease states.