Refinement and Validation of a Portable, Salivary Biosensor of Psychosocial Stres

描述(由申请人提供)：我们的跨学科申请直接响应RFA-DA-07-005(U01)的目标，建议对原型生物传感器进行改进、现场验证和技术扩展，以促进对暴露于系统性和心理社会应激源的唾液生物标记物的快速和准确测量。我们现有的手持式生物传感器利用一个微型光学平台和廉价的比色测试试纸来快速检测和定量唾液α-淀粉酶(SAA)，这是人体肾上腺素能应激反应的主要生物指标。与通常涉及侵入性采样和提供静态测量的精心设计的基于实验室的分析不同，瞬时唾液生物传感器允许具有时间和空间分辨率，有利于大规模人群研究压力与健康结果的相互作用。我们将首先在50名健康对照的队列中优化生物传感器的技术性能特征，方法是a)建立便携式SAA生物传感器的校准曲线，并将其与实验室检测的SAA进行比较；b)检查生物传感器的可靠性(精密度和准确度)；c)证明其作为暴露评估工具在低和高压力条件下的有效性。随后，我们将在185名全身(面部损伤)和心理应激程度较高的脆弱患者中进行小规模现场测试和功能验证。我们将a)测试SAA生物传感器在不同系统和心理社会压力(医院入院、术后10天、术后30天)下的收集程序和有效性，b)检查易感脆弱性(例如社会人口统计、压力负担、社会支持)和系统环境(例如物质使用、健康/生活方式行为)对生物标记物水平的潜在混淆影响，以及c)评估生物传感器SAA对创伤后适应不良心理(例如痛苦、焦虑、抑郁)和行为症状(例如物质使用增加)的预测有效性。同时，我们将完善生物传感器平台的技术能力，并扩大其能力，以允许对反映应激反应(例如皮质醇、脱氢表雄酮、睾酮)以及合法和非法物质使用的其他唾液分析进行多重分析。我们的最终目标是开发一个通用的、便携的平台，通过检测和可靠地量化相关的唾液反应指标，来操作压力和物质使用的心理生物学。互补的研究专业知识和致力于心理社会压力及其生物标记物的前身研究的协同结合，最大限度地提高了我们的研究计划在资助期结束前生产出可现场部署的压力反应生物传感器的可能性。

DESCRIPTION (provided by applicant): Our transdisciplinary application responds directly to the objectives of RFA-DA-07-005 (U01) by proposing the refinement, field validation and technical expansion of a prototype biosensor to facilitate rapid and precise measurement of salivary biomarkers of exposure to systemic and psychosocial stressors. Our extant hand-held biosensor utilizes a miniaturized optical platform and inexpensive, colorimetric test strips to rapidly detect and quantify salivary alpha-amylase (SAA), a primary bioindicator of the body's adrenergic stress response. Unlike elaborate, laboratory-based assays that frequently involve invasive sampling and provide static measurements, the instantaneous salivary biosensor allows a temporal and spatial resolution conducive to large-scale population studies of stress-health outcome interactions. We will first optimize the technical performance characteristics of the biosensor in a cohort of 50 healthy controls by a) establishing calibration curves for the portable SAA biosensor and comparing it to laboratory assayed SAA, b) examining biosensor reliability (precision and accuracy) over the diurnal cycle, and c) demonstrating its validity as a exposure assessment tool under conditions of low and high stress. Subsequently we will conduct small-scale field testing and functional validation of the biosensor in a cohort of 185 vulnerable patients with high systemic (facial injury) and psychosocial stress. We will a) test collection procedures and validity of the SAA biosensor across variations in systemic and psychosocial stress (hospital intake, 10 days post-surgery, 30-day post surgery), b) examine potential confounding effects of predisposing vulnerabilities (e.g., sociodemographics, stress burden, social support) and systemic milieu (e.g., substance use, health/lifestyle behaviors) on biomarker levels, and c) assess the predictive validity of biosensor SAA for maladaptive psychological (e.g., distress, anxiety, depression) and behavioral symptoms (e.g., increased substance use) following injury. Concurrently, we will refine the technical capabilities of the biosensor platform and expand its capabilities to permit multiplexed assays of other salivary analytes reflective of the stress response (e.g., cortisol, DHEA, testosterone) as well as licit and illicit substance use. Our ultimate goal is to develop a universal, portable platform to operationalize the psychobiology of stress and substance use by detecting and reliably quantifying relevant salivary response indicators. The synergistic combination of complementary research expertise and the body of precursor research devoted to psychosocial stress and its biomarkers maximize the likelihood that our research program will produce a field-deployable biosensor of the stress response by the end of the funding period.