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: 8129370
• 负责人: Manju Grover Venugopal
• 金额: $ 51.25万
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8129370
• 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. PUBLIC HEALTH RELEVANCE: We are proposing to make a tool for rapid detection of cortisol, called StressSmartTM. "InstaCortisolTM" (a rapid cortisol test developed during Phase I), will be integrated in StressSmart device to develop a portable test for real-time measurement of personal exposure to psychosocial stress via detecting cortisol in interstitial fluid (ISF). The new minimally invasive tool will enable researchers to quantify personal exposure to psychosocial stress, as experienced by individuals in real-life situations. This device will be capable of measuring cortisol quantitatively, selectively, objectively, reliably, and securely.

描述（由申请人提供）：重复暴露于心理社会压力与多种人类疾病（例如癌症、毒瘾、心脏病、抑郁症）相关，这些疾病造成了值得注意的公共健康负担。然而，我们的进展受到限制，因为缺乏一种便携式设备，该设备可以快速、可靠、非侵入性和连续地实时测量个人在自然环境中所经历的社会心理压力。尽管存在评估临床环境中心理社会压力暴露的可靠方法，但这些间歇性评估并不能准确描述暴露的时间、持续时间、频率或强度。目前美国有超过 3600 名注册内分泌科医生，平均每天转介 5 名患者进行皮质醇测试。该测试是通过将患者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“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，它将容纳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。我们的快速测试基于免疫电化学方法，其中使用基于二硫代双琥珀酰亚胺丙酸酯 (DTSP) 自组装单层 (SAM) 的皮质醇免疫传感器来测量反应信号。使用阻抗测量技术可以促进检测。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制造和传感器评估，包括灵敏度、特异性、检测限、线性、准确性、动态范围、重复性、精度、准确度、干扰、交叉反应、漂移和传感器校准。其次是微流控架构系统的发展。第三个目标是微流体阀的设计、制造、集成和开发。需要几个这样的阀门作为三个一次性筒的一部分。第四和第五个目标是开发可靠的真空微流体泵，然后将皮质醇传感器外壳开发为设备的一部分。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紧凑的易于使用的设计中将同时进行。对皮质醇传感器芯片及其集成到紧凑且易于使用的设计中的虚拟评估也将在整个第二年预算期间进行。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所经历的社会心理压力，就像个人在现实生活中所经历的那样。皮质醇的产生遵循昼夜节律，而且会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一次测量相比很重要。最近的研究调查显示，准确评估皮质醇一天所需的最少样本数量是五个。我们当前的一次性墨盒设计用于在 24 小时内收集四次测量结果以进行概念验证。然而，该设备可以轻松地重新设计，以适应任何其他临床相关要求。这种非侵入性快速皮质醇测量装置的出现将使患者能够在 24 小时内监测其皮质醇水平，并且专业人员能够在一天中的多个时间点修改给药方案。 公共健康相关性：我们提议制作一种快速检测皮质醇的工具，称为 StressSmartTM。 “InstaCortisolTM”（第一阶段开发的快速皮质醇测试）将集成到 StressSmart 设备中，以开发便携式测试，通过检测间质液（ISF）中的皮质醇来实时测量个人承受的心理压力。新的微创工具将使研究人员能够量化个人在现实生活中所经历的社会心理压力。该设备将能够定量、选择性、客观、可靠和安全地测量皮质醇。