Supramolecular Assemblies for Detecting Biomarkers in Complex Mixtures

描述（由申请人提供）：识别特定分子并报告其在复杂混合物中的存在是一项重大挑战，该提案概述了解决这一问题的新的超分子方法。由于在疾病的早期检测中的意义，在生理流体（例如血清）中检测小浓度的生物标志物已经引起了极大的兴趣。在这项提案中，我们专注于基于肽和蛋白质的生物标志物，其检测在癌症的早期诊断中具有重要意义-这是有效癌症治疗的关键因素。初步的结果是非常令人鼓舞的，这是至关重要的，我们进一步发展这种方法的现实生活中的系统，通过了解的因素，结合和检测事件。拟议的研究集中在这一目的。我们的方法的关键要素是：（i）我们的聚合物组装体在组装溶剂中被动力学捕获，并在广泛的条件下保持其超分子保真度;（ii）这些组装体与一组选择性的肽结合，以将它们从水相移动到有机相;（iii）我们的聚合物提供信号增强，大大提高了检测灵敏度;和（iv）所提出的实验方案允许同时灵敏地检测几种生物标志物。这些有前途的功能将被严格测试，用于检测复杂生理液体、血清和母乳中的癌症生物标志物。请注意，我们专注于完善的癌症生物标志物，使我们能够专注于测试新方法的多功能性。

DESCRIPTION (provided by applicant): Recognizing specific molecules and reporting their presence in a complex mixture is a significant challenge, and this proposal outlines a new supramolecular approach to address this problem. There has been a great interest in detecting biomarkers in small concentrations in physiological fluids, such as serum, because of the implications in early detection of diseases. In this proposal, we focus on peptide- and protein-based biomarkers, the detection of which is of interest in the early diagnosis of cancer - a criticl factor in effective cancer treatment. The preliminary results are very encouraging and it is essential that we further develop this approach for real-life systems by understanding the factors that underlie the binding and detection events. The proposed research is focused on this purpose. The key elements of our approach are that: (i) our polymer assemblies are kinetically trapped in the assembled solvent and maintain their supramolecular fidelity under a broad range of conditions; (ii) these assemblies bind to a selective set of peptides to move them from the aqueous to the organic phase; (iii) our polymers provide signal enhancements that greatly enhance the sensitivity of detection; and (iv) the proposed experimental protocols allow for concurrent detection of several biomarkers sensitively. These promising features will be rigorously tested for detecting cancer biomarkers in complex physiological fluids, serum and breast milk. Note that we focus on well-established cancer biomarkers to allow us to focus squarely on testing the versatility of new approach.