Instacortisol: A realtime and continuous assessment of cortisol in ISF

Instacortisol：ISF 中皮质醇的实时、连续评估

• 批准号: 8280328
• 负责人: Manju Grover Venugopal
• 金额: $ 54.15万
• 依托单位: GUIDED THERAPEUTICS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-13 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8280328
• 关键词: Addison' s disease; Adrenal Cortex; Affect; Algorithms; Anti-Bacterial Agents; Antineoplastic Agents; Autoimmune Diseases; Award; Behavioral Sciences; Biological; Biological Assay; Biological Markers; Biological Process; Biosensor; Budgets; Calibration; Circadian Rhythms; Clinical; Coagulation Process; Collection; Communities; Cushing Syndrome; Data; Data Collection; Detection; Development; Devices; Diet; Disease; Dose; Drug Addiction; Electronics; Endocrinologist; Environment; Epinephrine; Evaluation; Event; Exercise; Exposure to; Frequencies; Goals; Harvest; Heart Diseases; Hormones; Hour; Housing; Human; Hydrocortisone; Individual; Intake; Intercellular Fluid; Intervention; Investigation; Learning; Life; Measurement; Measures; Mental Depression; Methods; Microfluidics; Miniaturization; Monitor; Mothers; Nicotine; Nutrient; Obesity; Participant; Patients; Performance; Persons; Phase; Physical environment; Pilot Projects; Positioning Attribute; Post-Traumatic Stress Disorders; Process; Production; Propionates; Psychosocial Stress; Public Health; Publishing; Pump; Reaction; Research; Research Personnel; Sampling; Sensitivity and Specificity; Signal Transduction; Sleep; Smoker; Source; Sports Medicine; Steroids; Stress; Surveys; System; Techniques; Testing; Time; Vacuum; Vacuum Pumps; Validation; Veterans; Work; base; clinically relevant; cross reactivity; dehydroepiandrosterone; design; electric impedance; experience; field study; human disease; meetings; minimally invasive; monolayer; novel; programs; rapid detection; sensor; strength training; stressor; system architecture; tool; transmission process; trend; virtual

DESCRIPTION (provided by applicant): Repetitive exposures to psychosocial stress are associated with several human diseases (e.g., cancer, drug addiction, heart disease, depression) of noteworthy public health burden. However, our progress is limited by the lack of a portable device that can enable rapid, dependable, non-invasive and continuous measurement of personal exposure to psychosocial stress in real-time, as experienced by individuals in their natural environments. Although reliable methods to assess exposure to psychosocial stress in clinical settings exist, these intermittent assessments do not accurately portray timing, duration, frequency, or intensity of exposure. Currently there are more than 3600 registered endocrinologists in the US and on an average they refer five patients per day for cortisol tests. This test is ordered by sending patient's samples to the lab. Therefore, there is a grave need to develop a rapid test for cortisol so a "No-Stress Stress Measuring Device" can be developed. In this interdisciplinary Phase II project, we propose to develop a new device called "StressSmartTM", which will house a rapid test for cortisol developed during Phase I, namely InstaCortisolTM. Cortisol is the primary steroid produced and secreted by the adrenal cortex and is used as a reliable indicator of stress. Our rapid test is based on immunoelectrochemical method where the reaction signal is measured by using dithiobissuccinimidyl propionate (DTSP) self assembled monolayer (SAM) based immunosensor for cortisol. Detection is being facilitated using impedance measuring technique. There are six specific aims of this project. First is further refining and optimizing the cortisol sensor fabrication and sensor evaluation, including sensitivity, specificity, detection limit, linearity, accuracy, dynamic range, repeatability, precision, accuracy, interference, cross-reactivity, drift, and sensor calibration. Second is the development of microfluidic architecture system. The third aim would be the design, fabrication, integration and development of a microfluidic valves. Several such valves will be needed as parts of the three disposable cartridges. Fourth and fifth aim being the development of a reliable vacuum microfluidics pump, followed by cortisol sensor housing development as part of the device. Throughout the program, some other efforts will also include cortisol sensor clotting mitigation, cortisol sensor electronic Interface board development, cortisol sensor miniaturization efforts, clinical validation and the design integration feasibility. A virtual evaluation of cortisol sensor chip and its integration into a compact easy to use design will be carried out in parallel. A virtual evaluation of cortisol sensor chip and its integration into a compact easy to use design will also be carried out throughout the Year 2 budget period. Relevance: The InstaCortisolTM test (developed during Phase I), which will be part of StressSmartTM device during Phase II, will enable researchers to quantify personal exposure to psychosocial stress, as experienced by individuals in real-life situations. Cortisol production follows a circadian rhythm, and moreover it is affected by stimulatory events or nutrient intake, so it important to measure the trend of cortisol in a person versus taking a single measurement in one day as is done traditionally. Recent research surveys have revealed that the minimal number of samples needed in a day for an accurate assessment of cortisol is five. Our current disposable cartridge is designed to collect four measurements over 24 hours for the proof of concept. However, this device can be easily re-designed to include any other clinically relevant requirements. Availability of such a non-invasive and rapid cortisol measuring device will allow patients to be able to monitor their cortisol levels over 24 hours and professionals to be able to modify dosing regiments at multiple points throughout the day.

描述（由申请人提供）：反复暴露于心理社会压力与几种人类疾病有关（例如，癌症、毒瘾、心脏病、抑郁症）的公共卫生负担。然而，我们的进展受到缺乏便携式设备的限制，该设备可以实时快速，可靠，非侵入性和连续测量个人在自然环境中所经历的心理社会压力。虽然存在可靠的方法来评估在临床环境中暴露于心理社会压力，这些间歇性的评估不准确地描绘时间，持续时间，频率，或暴露的强度。目前，美国有超过3600名注册内分泌学家，平均每天有5名患者接受皮质醇测试。该测试是通过将患者的样本发送到实验室来订购的。因此，迫切需要开发一种快速检测皮质醇的方法，从而开发出一种“无压力压力测量装置”。在这个跨学科的第二阶段项目中，我们建议开发一种名为“StressSmartTM”的新设备，该设备将容纳在第一阶段开发的皮质醇快速测试，即InstaCortisolTM。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。我们的快速检测是基于免疫电化学方法，其中反应信号是通过使用二硫代双琥珀酰亚胺丙酸酯（DTSP）自组装单分子膜（SAM）为基础的免疫传感器皮质醇。正在利用阻抗测量技术促进检测。该项目有六个具体目标。首先是进一步完善和优化皮质醇传感器的制造和传感器评估，包括灵敏度、特异性、检测限、线性、准确度、动态范围、重复性、精密度、准确度、干扰、交叉反应性、漂移和传感器校准。二是微流控体系结构的发展。第三个目标是微流体阀的设计、制造、集成和开发。需要几个这样的阀作为三个一次性药筒的一部分。第四和第五个目标是开发可靠的真空微流体泵，然后是作为设备一部分的皮质醇传感器外壳开发。在整个计划中，其他一些工作还将包括皮质醇传感器凝血缓解、皮质醇传感器电子接口板开发、皮质醇传感器小型化工作、临床验证和设计集成可行性。皮质醇传感器芯片的虚拟评估及其集成到一个紧凑的易于使用的设计将并行进行。皮质醇传感器芯片的虚拟评估及其集成到一个紧凑的易于使用的设计也将在整个第二年的预算期间进行。相关性：InstaCortisolTM测试（在第一阶段开发）将成为第二阶段StressSmartTM设备的一部分，将使研究人员能够量化个人在现实生活中所经历的心理社会压力。皮质醇的产生遵循昼夜节律，而且它受到刺激事件或营养摄入的影响，因此测量一个人的皮质醇趋势与传统上在一天内进行单一测量是很重要的。最近的研究调查显示，一天中准确评估皮质醇所需的最少样本数量是5。我们目前的一次性检测盒设计用于在24小时内收集四次测量结果，以验证概念。但是，该器械可以很容易地重新设计，以满足任何其他临床相关要求。这种非侵入性和快速皮质醇测量设备的可用性将使患者能够在24小时内监测他们的皮质醇水平，并且专业人员能够在一天中的多个时间点修改给药方案。