Multianalyte physiological optical waveguide sensing

描述（由申请人提供）：背景。一般生物传感和生物医学相关化合物的多路传感分析物的特异性和灵敏度必须提高，以提供这些设备的临床应用。特别是，改善传感器信号和限制噪声是改进设计寻求的两个重要性能增强。这一建议的动机是我们的观察：(1)免疫生物传感代表了最常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)不同免疫传感阵列尺寸的分析物检出限；(3)亚微米光波导代表了这种传感方式的技术前沿；(4)减小光波导尺寸的优势是可行的，该传感器件的设计模式发生了转变。

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.