A multiplex panel for simultaneously profiling toxicant levels and biological res

描述(由申请人提供)：暴露科学领域对自上而下研究人类环境暴露(暴露组)的方法越来越感兴趣，在这种方法中，感兴趣的毒物通过血液和/或其他生物样本在体内进行剖析。这类研究将补充更传统的自下而上的方法，即对个人生活的环境进行采样和研究，以确定潜在的致病原因。这项应用中提出的工作的长期目标是创造高度多元化的传感器，不仅有助于检测血清样本中的环境毒物，而且还可以分析这些潜在暴露引起的免疫或其他生物反应。通过NIEHS资助的以前的工作，Adarza BioSystems开发了一种便携式、多路蛋白质检测系统，旨在描述手指棒体积血液中有毒物质暴露的生物反应。通过测量细胞因子和其他蛋白质生物标志物的水平，可以使用该工具在现场快速评估与炎症、氧化应激和凝血相关的健康状态信息，而不需要中央实验室设施。在这项应用中，我们首次寻求将这一核心检测技术应用于与人类疾病有关的环境毒物的直接检测。具体地说，将在第一阶段开发针对双酚A、三氯生、苯并[a]芘、萘和氯丹的5-丛阵列。AIM 1将开发所需的功能阵列探针，用于优化AIM 2中的分析方案。然后，将在AIM 3中测量所有目标化合物的检测灵敏度。在未来的第二阶段工作中，这一示范阵列将扩展为额外的毒物含量，并添加到Adarza现有的环境响应生物标记物中，创建一个单一的检测平台，将同时描述已知毒物及其从一滴血中的生物反应。

DESCRIPTION (provided by applicant): There is increasing interest in the exposure science field in top-down approaches to studying human environmental exposures (the exposome), where toxicants of interest are profiled within the body through blood and/or other biological samples. Such studies would complement more traditional bottom-up approaches where the environment in which an individual lives is sampled and studied to identify potential causes of disease. The long-term goal of the work proposed in this application is to create highly multiplex sensors to facilitate not only the detection of environmental toxicants in serum samples, but to also profile the immune or other biological response induced by these potential exposures. Through previous work funded by the NIEHS, Adarza BioSystems has developed a portable, multiplex protein detection system designed to profile biological response to toxic exposures from a finger-stick volume of blood. By measuring the levels of cytokines and other protein biomarkers, health status information related to inflammation, oxidative stress, and coagulation can be quickly assessed in the field using this tool, without the need for centralized laboratory facilities. In this application we seek to apply this core detection technology for the first time,to the direct detection of environmental toxicants linked to human disease. Specifically, a 5-plex array will be developed in Phase I that will target Bisphenol A, Triclosan, Benzo[a]pyrene, Napthalene, and Chlordane. Aim 1 will develop the required functional array probes that will be used to optimize the assay protocol in Aim 2. The detection sensitivity for all target compounds will then be measured in Aim 3. In a future Phase II effort, this demonstration array will be expanded with additional toxicant content and added to Adarza's existing environmental response biomarkers, creating a single detection platform that will simultaneously profile known toxicants and their biological response from a single drop of blood.