A multiplex panel for simultaneously profiling toxicant levels and biological res

描述（由申请人提供）：暴露科学领域越来越关注自上而下的方法来研究人类环境暴露（暴露体），其中感兴趣的毒物通过血液和/或其他生物样本在体内进行分析。这种研究将补充更传统的自下而上的方法，在这种方法中，对个人生活的环境进行抽样和研究，以确定疾病的潜在原因。本应用中提出的工作的长期目标是创建高度多路传感器，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。通过此前由NIEHS资助的工作，Adarza BioSystems开发了一种便携式、多重蛋白质检测系统，旨在分析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，使用该工具可以在现场快速评估与炎症、氧化应激和凝血相关的健康状况信息，而不需要集中的实验室设施。在这项应用中，我们寻求首次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。具体来说，第一阶段将开发一个5-plex阵列，该阵列将针对双酚a、三氯生、苯并芘、萘和氯丹。目标1将开发所需的功能阵列探针，用于优化目标2的分析方案。所有目标化合物的检测灵敏度将在Aim 3中测量。在未来的II期工作中，该演示阵列将扩展额外的毒物含量，并添加到Adarza现有的环境反应生物标志物中，创建一个单一的检测平台，可以同时从一滴血中分析已知的毒物及其生物反应。

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.