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）的空气中颗粒物（PM）无处不在。然而，自工业革命以来的人类活动和内燃机的出现大大增加了PM的浓度，特别是在城市地区。人体来源的PM往往尺寸较小，便于通过呼吸道和消化道以及通过皮肤进入体内。它还往往具有吸附的化学物种，其毒性比天然对应物更大。纳米技术在研究和消费品（防晒霜，化妆品，油漆）中的爆炸性增长也创造了一系列超细材料，这些材料对健康的影响基本上是未知的。尽管许多研究表明PM与各种疾病有关，包括急性呼吸道感染、肺癌、慢性呼吸道和心血管疾病，但所涉及的具体生物学机制尚未完全了解。Adarza BioSystems，Inc.该公司试图利用其专有的阵列成像反射仪（AIR）生物传感平台来构建一种能够快速捕获对PM暴露的详细生理反应的设备，该设备通过分析方便获得的生物样品（例如手指采集的血液、尿液、粘液、唾液等）中的关键标记蛋白（可能>100）来实现。AIR能够用目前笔记本电脑大小的设备进行灵敏和同步的蛋白质检测。该提案的目标是将我们的多重实验室检测方法密封在一个保护性塑料盒中，以便在不可预测和无保护的环境中进行现场工作。我们打算与一家在建立符合军事规格的便携式生物测定方面有着长期记录的公司合作，以促进这一开发工作。改进的光学读取器也将被设计成具有集成处理单元以控制盒内的流体操作。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份样本库进行检测，以验证AIR生物测定系统的性能。在这个为期2年的项目结束时，我们打算有一个现场部署的原型和检测盒，准备用于大规模人群研究。 公共卫生相关性：颗粒物（PM）是环境医学领域的一个主要问题，因为通过空气、水或接触小颗粒是不可避免的，并且已知这些材料通过呼吸道和消化道甚至通过皮肤进入人体。暴露于PM与各种呼吸系统、炎症和心脏疾病有关，但其潜在机制尚不清楚。Adarza生物系统公司该公司试图将其快速和高度多路复用的蛋白质谱分析技术整合到一个可现场部署的系统中，该系统能够在大规模人群研究中测量参与者对颗粒物或其他环境应激源的生理反应。

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.