A rapid label-free sensor for immune markers of environmental exposure for applic

描述（由申请人提供）：来自各种自然来源（火山活动，森林火灾）的空气悬浮颗粒物（PM）无处不在。然而，自工业革命和内燃机出现以来，人类活动大大增加了PM的浓度，特别是在城市地区。人体来源的PM往往体积较小，便于通过呼吸道和消化道以及皮肤进入人体。它还倾向于吸附比其天然对应物毒性更大的化学物质。纳米技术在研究和消费产品（防晒霜、化妆品、油漆）中的爆炸式增长，也创造了一系列对健康有很大未知影响的超细材料。尽管大量研究表明PM与各种疾病包括急性呼吸道感染、肺癌、慢性呼吸道和心血管疾病有关，但所涉及的具体生物学机制尚未完全了解。Adarza BioSystems, Inc.寻求利用其专有的阵列成像反射法（AIR）生物传感平台，建立一种能够快速捕获PM暴露详细生理反应的设备，通过分析可方便获得的生物样品（如手指采集的血液、尿液、粘液、唾液等）中的关键标记蛋白（可能达到100个）。目前，这样的测试需要几个小时，而且通常是单独的单路测试。AIR能够使用目前笔记本电脑大小的设备进行敏感和同步的蛋白质检测。本提案的目标是采用我们的多路实验室分析，并将其密封在保护性塑料盒中，以便在不可预测和无保护的环境中进行实地工作成为现实。我们打算与一家在军用规格便携式生物检测方面有着悠久历史的公司合作，以促进这一开发工作。一个改进的光学阅读器也将设计一个集成的处理单元，以控制墨盒内的流体操作。最后，将使用新开发的AIR生物测定法和更标准的实验室测定法对先前人群研究中使用的约1800个样本进行测试，以验证AIR生物测定系统的性能和性能。在这个为期2年的项目结束时，我们打算有一个现场可部署的原型和化验盒，为大规模的人口研究做好准备。

DESCRIPTION (provided by applicant): Airborne particulate matter (PM) derived from a variety of natural sources (volcanic activity, forest fires) is omnipresent. However, human activity since the industrial revolution and the advent of the internal combustion engine has substantially increased the concentration of PM, particularly in urban areas. Human derived PM tends to be of smaller size, facilitating entry into the body through the respiratory and digestive tracts, as well as through the skin. It also tends to have adsorbed chemical species with greater toxicity than its natural counterparts. The explosive growth of nanotechnology in research and consumer products (sunscreens, cosmetics, paint) is also creating an array of ultrafine materials with largely unknown health effects. Despite numerous studies implicating PM in various disorders including acute respiratory infections, lung cancer, and chronic respiratory and cardiovascular diseases, the specific biological mechanisms involved are not fully understood. Adarza BioSystems, Inc. seeks to leverage its proprietary Arrayed Imaging Reflectometery (AIR) biosensing platform to build a device capable of rapidly capturing the detailed physiological response to PM exposure by profiling key marker proteins (potentially >100) in conveniently available biosamples such as a finger pick of blood, urine, mucous, saliva, etc. Currently, such testing takes hours and is often done with individual singleplex tests. AIR is capable of sensitive and simultaneous protein detection with a device that is currently the size of a laptop computer. The goal of this proposal is to take our multiplexed laboratory assay, and seal it in a protective plastic cartridge so that fieldwork in unpredictable and unprotected environments would become realistic. We intend to collaborate with a company that has a long track record in building portable bioassays to military specifications to facilitate this development effort. An improved optical reader will also be designed with an integrated processing unit to control fluidic operations within the cartridge. Finally, a bank of ~1800 samples used in the previous population study will be tested using both the newly developed AIR bioassay and a more standard laboratory assay to verify the performance and of the AIR bioassay system. By the end of this 2-year project we intend to have a field deployable prototype and assay cartridges that are ready for large population studies. PUBLIC HEALTH RELEVANCE: Particulate matter (PM) is a major concern in the field of environmental medicine because exposure to small particles through air, water, or contact is unavoidable and these materials are known to enter the body through the respiratory and digestive tract, and even through skin. Exposure to PM has been linked to a variety of respiratory, inflammatory, and cardiac disorders, but the underlying mechanisms are not well understood. Adarza Biosystems, Inc. seeks to integrate its rapid and highly multiplexed protein profiling technology, in a field- deployable system capable of measuring a participant's physiological response to particulate matter or other environmental stressors in large population studies.