Electro-Optically Modulated SPR: Densely Multiplexed High-Sensitivity Biosensor

电光调制 SPR：密集多重高灵敏度生物传感器

• 批准号: 8592988
• 负责人: Mani Hossein-Zadeh
• 金额: $ 24.19万
• 依托单位: INTELLIGENT OPTICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8592988
• 关键词: Address; Area; Binding; Binding Proteins; Binding Sites; Biochemical; Biosensing Techniques; Biosensor; Cereals; Computer software; DNA; Data; Deposition; Detection; Devices; Employment; Engineering; Enhancers; Evaluation; Fluorescence; Glass; Goals; Government; Hand; Image; Imaging Device; Kinetics; Label; Laboratories; Lead; Left; Light; Measurement; Measures; Medical; Methods; Modeling; Molecular; Optics; Performance; Persons; Phase; Polymers; Property; Proteins; Radiation; Reader; Records; Refractive Indices; Research; Risk; Sampling; Scanning; Site; Small Business Innovation Research Grant; Speed; Spottings; Structure; Surface; Surface Plasmon Resonance; System; Techniques; Technology; Testing; Time; Work; base; biochip; biohazard detection; density; design; detector; drug discovery; improved; indexing; instrument; meetings; novel strategies; point of care; public health relevance; simulation; voltage

DESCRIPTION (provided by applicant): The overall objective of this Fast Track project is to develop products based on a technique that radically alters the way a mature biosensor technology - surface plasmon resonance (SPR) - is used. This new approach has the potential to dramatically improve SPR throughput for drug discovery, and could lead to the creation of practical hand-held SPR biosensors. Phase I will show that modifying the conventional SPR "stack" by adding an extra layer with an electronically controlled refractive index creates a structure in which plasmon resonance can be detected at a fixed angle, even as analyte binding changes the refractive index at the top of the stack. This solves a problem that has bedeviled SPR biosensors for more than 20 years: the fundamental incompatibility of angle-based measurement with SPR imaging of high spot-count (100's or 1,000's) biochips. Phase I will also demonstrate, by applying a time-varying voltage to the electro-optic (E-O) layer, and thereby modulating the resonance condition, synchronous detection of biomolecular binding using SPR. This also represents a significant advance, since it will enable the employment of a wide variety of sensitivity-enhancing techniques hitherto impossible, or extremely impractical, using other SPR detection approaches. Phase II will build on the Phase I demonstration of the fundamental advantages of index-modulated surface plasmon resonance (MSPR) detection. This phase will culminate in the creation and characterization of a complete system that produces real-time SPR sensograms from hundreds of biorecognition sites on a single chip simultaneously. This will be achieved by imaging the surface of the chip onto a CMOS detector array and rapidly scanning the index of the E-O layer. When the E-O layer's index gets to a value for which the "stack" together with a biospot reaches resonance, the image of that spot will disappear. By recording the bias voltage at which a particular spot's image disappears, its refractive index can be unambiguously determined. Thus, each time the MSPR array's E-O layer is swept, a complete image of the refractive index on the surface will be created. Because no "angular fan-out" is required to detect resonance, biorecognition spots can be packed very closely on the surface -virtually at the same density as for label-based systems. "Dithering" the E-O bias voltage during the sweep will have the effect of modulating the resonance condition directly at the binding site, allowing the use of "lock-in" detection, which can potentially increase refractiv index sensitivity by an order of magnitude or more over the already-impressive ?n < 10-7 achieved by the commercial Biacore device.

描述(由申请人提供)：这个快速通道项目的总体目标是开发基于一种技术的产品，该技术从根本上改变了成熟的生物传感器技术-表面等离子体共振(SPR)-的使用方式。这种新方法有可能极大地提高药物发现的SPR吞吐量，并可能导致实用的手持SPR生物传感器的创建。第一阶段将表明，通过增加具有电子控制折射率的附加层来修改传统的SPR“堆栈”，创建了一种结构，其中可以以固定的角度检测等离子激元共振，即使分析物结合改变了堆栈顶部的折射率。这解决了困扰SPR生物传感器20多年的一个问题：基于角度的测量与高点计数(100‘S或1,000’S)生物芯片的SPR成像根本不兼容。第一阶段还将演示，通过向电光(E-O)层施加随时间变化的电压，从而调制共振条件，使用SPR同步检测生物分子结合。这也代表着一项重大进步，因为它将使迄今为止不可能或非常不切实际的各种提高灵敏度的技术使用其他SPR检测方法。第二阶段将建立在第一阶段演示指数调制表面等离子体共振(MSPR)检测的基本优势的基础上。这一阶段的高潮将是创建和表征一个完整的系统，该系统在单个芯片上同时产生数百个生物识别点的实时SPR传感图像。这将通过将芯片表面成像到cmos探测器阵列上并快速扫描E-O层的索引来实现。当E-O层的索引达到一个值时，“堆叠”和一个生物点就会达到共振，那个点的图像就会消失。通过记录特定光点的图像消失时的偏置电压，可以明确地确定其折射率。因此，每次扫描MSPR阵列的E-O层时，将创建表面上折射率的完整图像。因为不需要“角度扇形”来检测共振，所以生物识别斑点可以非常紧密地堆积在表面--几乎以与基于标签的系统相同的密度。在扫描过程中“抖动”E-O偏置电压将具有直接在结合部位调制共振条件的效果，允许使用“锁定”检测，这可能会将折射率灵敏度提高一个数量级或更多，超过商用Biacore设备已经达到的令人印象深刻的？N&lt；10-7。