Enhanced Liquid Core Waveguide Biosensor for PBDE Detection

描述（由申请人提供）：多溴联苯醚（PBDEs）是一种常见的阻燃剂，用于降低各种产品的火灾风险，如床垫、家具、家用电子产品、纺织品、室内装饰织物、地毯和儿童玩具。因此，已发现该物质在环境中广泛传播，并通过各种接触途径发生生物蓄积，由于其对人类健康的潜在不利影响，对公众健康构成关切。在这方面，迫切需要开发一种现场便携式快速“现场”检测方法，用于早期诊断人类接触或环境监测。为了满足这一需求，Synthia-LLC公司提议开发一种用于检测BDE-47（毒性最强的多溴二苯醚同系物之一）的现场便携式生物传感器。使用被称为噬菌体抗免疫复合物测定（PHAIA）的专利技术，这是一种基于分析物-抗体复合物特异性噬菌体携带肽的多功能非竞争性双位点测定形式，作为关键技术，Synthia-LLC将通过设定三个目标来实现目标，开发液芯波导中的均匀荧光能量转移PHAIA（FRET PHAIA-LCW）。第一个目标是通过利用噬菌体颗粒的聚结合性质开发基于标准386孔板的均质FRET PHAIA。我们预期，通过与镧系元素供体以高密度缀合的单个噬菌体颗粒和用受体染料标记的许多抗体之间的多重相互作用的有效荧光能量转移不仅将增强信号强度，导致更好的灵敏度，而且缩短一般测定时间，因为不需要重复洗涤和孵育。第二个目标是建立一种简单的生物样品提取方法。我们预期，简单的提取方法将消除任何可能导致假阳性或假阴性结果的基质效应，从而提高测定的检测准确度。第三个目的是在一个简单的设备设计的FRET PHAIA-LCW的可行性测试。对于阶段I，将使用市售的液芯波导单元进行该测试。我们期望LCW在以最小的信号损失将荧光信号引导到检测器的特性将进一步提高测定灵敏度，并且液相测定可以容易地扩展到自动化紧凑型装置。 公共卫生相关性：Synthia-LLC提出的分析装置最终将是一种快速、现场便携式装置，可用于精确测量人类在环境中接触多溴二苯醚阻燃剂的情况。精确的测量信息可用于减少接触，从而减少这些有毒化合物的风险。

DESCRIPTION (provided by applicant): Polybrominated diphenyl ethers (PBDEs) are common flame retardants used to reduce the risk of fire in a wide variety of products, such as mattresses, furniture, home electronics, textiles, upholstery fabrics, carpet, and children's toys. As a consequence, wide spread occurrence in the environment and bioaccumulation through various exposure routes have been revealed posing concerns to public health because of their potential adverse effects on human health. In this respect, there is a high demand to develop a field-portable rapid "on-site" detection method for early diagnosis of human exposure or environmental monitoring. In order to meet this need, Synthia-LLC proposes the development of a field-portable biosensor for BDE-47, one of the most toxic PBDE congeners. Using patented technology referred to as a phage anti-immunocomplex assay (PHAIA) which is a versatile non-competitive two site assay format for small compounds based on an analyte-antibody complex specific phage-borne peptide as the key technology, Synthia-LLC will develop a homogeneous fluorescent energy transfer PHAIA in a liquid core waveguide (FRET PHAIA-LCW) by setting three aims to achieve the goal. The first aim is the development of a standard 386-well plate based homogeneous FRET PHAIA by taking advantage of the poly binding nature of the phage particle. We expect that efficient fluorescent energy transfer through multiple interactions between an individual phage particle conjugated with the lanthanide donor in high density and many antibodies labeled with acceptor dye will not only enhance signal intensity, resulting in better sensitivity, but shorten general assay time because there is no need for repeated washing and incubation. The second aim is the establishment of a simple sample extraction method from biological samples. We expect that the simple extraction method will eliminate any matrix effect that may cause a false positive or negative result and thus enhance the detection accuracy of the assay. The third aim is a feasibility test of the FRET PHAIA-LCW in a simple device design. For Phase I, this test will be carried out using a commercially available liquid core waveguide cell. We expect that the property of the LCW in guiding the fluorescent signals to the detector with minimal signal loss will further enhance the assay sensitivity and the liquid phase assay can be easily extended to an automated compact type device. PUBLIC HEALTH RELEVANCE: The assay device proposed by Synthia-LLC will ultimately be a rapid, field portable device that can be used to provide precise measures of environmental exposure of humans to polybrominated diphenyl ether flame retardants (PBDEs). Precise measurement information can then be used to reduce exposures and thus risk of these toxic compounds.