Multianalyte physiological optical waveguide sensing

描述（由申请人提供）：背景。分析物的特异性和灵敏度的生物传感一般和生物医学相关的化合物的多重传感必须加以改善，以提供这些设备的临床实用性。特别地，在限制噪声的同时改善传感器信号是改进设计所寻求的两个重要的性能增强。该提议的动机是我们的观察：（1）免疫生物传感代表了最常用的开发和开发的生物分析设备，用于非侵入性和侵入性生物医学诊断;（2）分析物的检测限与免疫传感阵列尺寸成比例;（3）亚微米光波导代表了这种传感模式的技术前沿;（4）减小光波导中的尺寸尺度的优点是可行的，在该感测装置设计中具有范例转换。 假说.为了解决这些挑战，我们提出了我们的工作假设，即在复杂环境中（例如，生理流体、唾液和血清）将通过将新的光学传感模式与传感元件的小型化集成到亚微米尺度来获得。这一假设涉及到整合的问题，设备规模（运输，阵列，光学报告）与新的光波导设备的方式适合传感结构制造在这个规模 具体目标。为了检验和验证我们的假设，我们提出了以下五个具体目标： 目的1：从光学理论出发，确定该模型中的无试剂倏逝波检测模式; 目标二：使用流体输运理论来支持快速响应和检测动力学以及波导传感性能增强，预期该设备在这些小尺寸（亚微米）光学和流体机械尺度下运行; 目标3：基于一种新的亚微米波导方法和对不同分析物具有特异性的微阵列免疫探针区域，建立功能原型集成光波导传感装置; 目标4：将NSOM远场光学作为检测技术集成到波导器件中，用于亚微米倏逝波传感; 目标5：在与生理传感相关的复杂流体环境中使用该设备，为四种模型分析物类别（小分子、蛋白质、病毒和DNA）的灵敏度限值、检测和动力学响应建立工作生物分析定义。

DESCRIPTION (provided by applicant): Background. Analyte specificity and sensitivity for biosensing in general and multiplexed sensing of biomedically relevant compounds must be improved to provide clinical utility for these devices. In particular, improvement of sensor signal while limiting noise are two important performance enhancements sought with improved designs. This proposal is motivated by our observations that (1) immunobiosensing represents the most commonly exploited and developed bioanalytical device for non-invasive and invasive biomedical diagnosis; (2) detection limits for analytes scale with immunosensing array size; (3) submicron optical waveguides represent a technical frontier for this sensing modality; (4) advantages of reducing size scale in optical waveguides are feasible with a paradigm shift in this sensing device design. Hypothesis. To address these challenges, we propose our working hypothesis that increased bioananalyte sensitivity and device response for multianalyte sensing in complex milieu (e.g., physiological fluids, saliva, and serum) will be gained by integrating a new optical sensing mode with miniaturization of sensing components to the sub-micron scale. This hypothesis involves integrating issues of device scale (transport, arraying, optical reporting) with new optical waveguide device modalities appropriate for sensing constructs fabricated in this size scale Specific Aims. To test and validate our hypothesis, we propose the following five Specific Aims: Aim 1: Define by optical theory a mode for reagentless evanescent detection in this model; Aim 2: Use fluid transport theories to support rapid response and detection kinetics and waveguide sensing performance enhancements expected for this device operating in these small size (sub-micron) optical and fluid mechanical scales; Aim 3: Establish a functional prototype integrated optical waveguide sensing device based on a new submicron waveguide method and microarrayed immunoprobe regions specific for different analytes; Aim 4: Integrate NSOM far-field optics as a detection technology into a waveguide device for sub-micron evanescent sensing; Aim 5: Establish working bioanalytical definitions for sensitivity limits, detection, and kinetic response for four model analyte classes--small molecules, proteins, viruses, and DNA--using this device in complex fluid milieu relevant to physiological based sensing.