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）：对社会心理压力的重复暴露与值得注意的公共卫生负担的几种人类疾病（例如癌症，药物成瘾，心脏病，抑郁症）有关。但是，我们的进步受到缺乏便携式设备的限制，该设备可以实时快速，可靠，无创和连续地测量个人对社会心理压力的暴露，就像个人在自然环境中所经历的那样。尽管存在评估临床环境中心理压力暴露的可靠方法，但这些间歇性评估并未准确地描绘暴露的时间，持续时间，频率或强度。目前，美国有3600多家注册的内分泌学家，平均每天将五名患者推荐用于皮质醇测试。该测试是通过将患者的样本发送到实验室来订购的。因此，需要对皮质醇进行快速测试，因此可以开发“无压力测量装置”。在这个跨学科的II阶段项目中，我们建议开发一种称为“ ResenceMarttm”的新设备，该设备将对在I期中开发的皮质醇进行快速测试，即Instacortisoltm。皮质醇是由肾上腺皮质产生和分泌的主要类固醇，用作可靠的胁迫指标。我们的快速测试基于免疫电化学方法，其中通过使用基于皮质醇的基于基于基于的单层的单层（SAM）的自由丙酰丙酸酯（DTSP）自组装单层（SAM）进行反应信号。使用阻抗测量技术促进了检测。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，检测极限，线性，准确性，动态范围，可重复性，精度，准确性，干扰性，交叉反应性，漂移和传感器校准。第二是微流体体系结构系统的开发。第三个目标是微流体阀的设计，制造，整合和开发。将需要几个这样的阀作为三个一次性墨盒的一部分。第四和第五的目标是开发可靠的真空微流体泵，然后是皮质醇传感器外壳开发作为该设备的一部分。在整个程序中，其他一些努力还将包括皮质醇传感器凝结缓解，皮质醇传感器电子接口板的开发，皮质醇传感器微型化工作，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整合到紧凑型易于使用的设计中，将并行进行。皮质醇传感器芯片的虚拟评估及其整合到紧凑型易于使用的设计中也将在2年预算期间进行。相关性：Instacortisoltm测试（在I期中开发）（在II阶段期间将是压力玛特设备的一部分），将使研究人员能够量化个人在现实生活中的个人所经历的个人对社会心理压力的暴露。皮质醇的产生遵循昼夜节律，此外，它受刺激事件或营养摄入的影响，因此，与传统上那样，测量一个人的皮质醇趋势与单一测量的趋势非常重要。最近的研究调查表明，每天需要对皮质醇进行准确评估所需的样品数量最少为五。我们当前的一次性弹药筒旨在在24小时内收集四个测量值以进行概念证明。但是，可以轻松地重新设计该设备，以包括任何其他与临床相关的要求。这种非侵入性和快速皮质醇测量装置的可用性将使患者能够在24小时内监测其皮质醇水平，并且专业人员能够全天在多个点上修改给药团。 公共卫生相关性：我们提议为快速检测皮质醇（称为stressmarttm）制造一种工具。 “ Instacortisoltm”（在I期中开发的快速皮质醇测试）将集成到应力玛特装置中，以开发可移植测试，以实时测量个人对心理压力的个人暴露，通过检测间质体液中的皮质醇（ISF）。新的微创工具将使研究人员能够量化个人对社会心理压力的暴露，就像个人在现实生活中所经历的那样。该设备将能够定量，有选择地，客观，可靠和安全地测量皮质醇。