Development of Distributed Feedback Laser Biosensor Technology as a High Resoluti

描述（由申请人提供）：该提案描述了一种全新类型的光学生物传感器的初步开发，该生物传感器利用基于塑料的激光表面结构主动产生光输出，以提供生物分子相互作用的高分辨率无标记传感。虽然激光生物传感器可以通过复制成型工艺在大的表面积上廉价地生产，但是我们建议构建的检测仪器将是紧凑的、廉价的，并且能够具有足够的分辨率以直接检测小分子结合到具有高信噪比的固定化蛋白质靶。这里提出的第一个资助的努力，将使传感器制造过程的发展，检测仪器的建设，和性能的一组小分子直接结合测定的初步可行性研究。我们的长期目标是将这种生物传感器方法开发成一种通用的检测平台，用于小分子筛选，基于细胞的测定，生物标志物诊断和环境检测，利用其成像检测和单蛋白分子检测分辨率的潜力。 公共卫生相关性：拟议的项目旨在开发一种高分辨率的生物分子相互作用检测技术，该技术可用于解决由没有酶功能的蛋白质组成的蛋白质组的大范围，因此使用传统技术无法“筛选”。调节转录的蛋白质，那些从细胞表面接收信号的蛋白质，以及那些参与DNA损伤修复的蛋白质，是成千上万种不具有酶活性的蛋白质中的一种，但其与药物的调节可能导致对许多疾病的治疗。新蛋白质靶点数量的停滞强调了对高通量筛选新技术的需求：从1989年到2000年，只有6%的新分子实体击中了以前未被破坏的靶点。因此，为了找到新的靶点并鉴定在疾病治疗中真正取得突破的新化合物，我们需要可用于快速鉴定蛋白质小分子结合剂的检测方法，而不仅仅是酶抑制剂。

DESCRIPTION (provided by applicant): The proposal describes the initial development of a fundamentally new type of optical biosensor that utilizes active generation of light output with a plastic-based laser surface structure to provide high resolution label-free sensing of biomolecular interactions. While the laser biosensor can be produced inexpensively over large surface areas by a replica molding process, the detection instrument that we propose building will be compact, inexpensive, and capable of resolution sufficient for direct detection of small molecule binding to immobilized protein targets with high signal-to-noise ratio. The first funded effort, proposed here, would enable development of the sensor fabrication process, construction of a detection instrument, and performance of a set of initial feasibility studies for small molecule direct binding assays. Our long-term goal is to develop this biosensor method into a general-purpose detection platform for small molecule screening, cell-based assays, biomarker diagnostics, and environmental detection by taking advantage of its potential for imaging detection and single protein molecule detection resolution. PUBLIC HEALTH RELEVANCE: The proposed project is aimed at the development of a high resolution biomolecular interaction detection technology that can be utilized to address the large swath of the proteome consisting of proteins that have no enzymatic function and are hence not "screenable" using conventional technologies. Proteins that modulate transcription, those that receive signals from the cellular surface, and those that are involved in DNA damage repair are among the thousands of proteins that do not have enzymatic activity but whose modulation with drugs could lead to treatments for a host of diseases. The stagnation in the number of new protein targets underscores the need for new technologies for high-throughput screening: in the years from 1989-2000, only 6% of the new molecular entities hit previously undrugged targets. Thus, to get at new targets and identify new compounds that are true breakthroughs in disease treatment, we need detection methodologies that can be utilized to rapidly identify small molecule binders for proteins, not merely enzymatic inhibitors.