Multianalyte physiological optical waveguide sensing

简介(申请人提供)：背景。分析物的特异性和对生物传感的灵敏度以及对生物医学相关化合物的多重传感必须得到提高，以便为这些设备提供临床应用。特别是，在限制噪声的同时改善传感器信号是通过改进设计寻求的两个重要的性能增强。这一建议的动机是我们观察到：(1)免疫生物传感是最常用和开发的用于非侵入性和侵入性生物医学诊断的生物分析设备；(2)免疫传感器阵列大小对分析物尺度的检测极限；(3)亚微米光波导是这种传感模式的技术前沿；(4)通过这种传感设备设计的范式转变，减小光波导尺寸的优势是可行的。 假设。为了应对这些挑战，我们提出了我们的工作假设，即在复杂环境(如生理液体、唾液和血清)中，通过将新的光学传感模式与传感元件微型化到亚微米级相结合，将提高生物分析物的灵敏度和设备对多分析物的响应。这一假设涉及将器件规模(传输、阵列、光学报告)的问题与适用于以这种尺寸制造的构造的传感的新的光波导器件形式相结合 明确的目标。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：用光学理论定义该模型中的一种无试剂消逝探测模式； 目的2：使用流体传输理论支持该器件在这些小尺寸(亚微米)光学和流体机械尺度下运行时预期的快速响应和检测动力学以及波导传感性能的增强； 目的3：建立一种基于新型亚微米波导法和针对不同分析物的微阵列免疫探针区的集成光波导传感装置的功能样机； 目的4：将NSOM远场光学作为探测技术集成到用于亚微米衰逝传感的光波导器件中； 目的5：在与基于生理的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--建立有效的生物分析定义，用于灵敏度极限、检测和动力学响应。

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.