High-content Label-free Electro-optic Surface Plasmon Resonance Assay Platform

描述（由申请人提供）：第一阶段 SBIR 提案的目标是开发一种基于表面等离子共振 (SPR) 的新型仪器平台，如果经过验证，将大大提高这种无标记技术对在系统生物学研究中利用高内涵分析的研究人员的实用性。该平台的优势源自检测范式的变化，允许对 SPR 位移作为电压函数进行固态测量。通过摆脱角度扫描或波长扫描方法，所提出的专有电光光栅耦合 SPR 平台 (EOSPR) 将同时研究多达 100,000 个感兴趣区域的束缚质量变化。与当前仪器相比，灵敏度的提高预计将比当前最先进的无标签技术有所提高，因为所提出的系统中的数据收集将比其他高容量设备中的数据收集速度明显更快。将附加数据纳入平均测量意味着更高的信噪比，但 EOSPR 系统还具有其他 SPR 平台所不具备的更多优势。只能在扫描速度与 EOSPR 设备一样快的系统上实施的信号斩波方案有望降低仪器的噪声。更好的信号和降低的噪声的结合预计将导致无标记检测灵敏度的提高，接近基于标记的技术的灵敏度。此外，由于 SPR 曲线的扫描可以比传统设备更快地完成，因此可以直接测量更快速的结合事件。验证该技术是否可以转化为商业产品所需的步骤包括：对拟议芯片进行建模、制造芯片、修改 Ciencia 先前设计的现有 SPR 仪器，以及在原型系统上进行概念验证实验。本提案正文概述了完成这些任务的目标，并将采用战略咨询安排和分包合同，以最大限度地提高这一潜在高影响力项目的成功可能性。 公共健康相关性：生物医学研究的当前趋势意味着医学的未来将依赖于不断提高的个性化治疗程度。随着了解的疾病状态和治疗方案的数量增加，做出明智决定所需的诊断信息量也在增加。拟议的 EOSPR 技术旨在通过满足对敏感、无标记和高含量检测的需求，并且价格足够可承受以供广泛采用，从而帮助系统生物学研究人员阐明和理解这些复杂的分子机制。

DESCRIPTION (provided by applicant): The objective of this Phase I SBIR proposal is the development of a novel instrumentation platform based on Surface Plasmon Resonance (SPR) that if validated would greatly increase the utility of this label-free technology to researchers utilizing high-content assays in systems biology investigations. The benefits of this platform derive from a change in detection paradigm that permits solid-state measurements of SPR shifts as a function of voltage. By moving away from an angle-scanning or wavelength-scanning approach, the proposed proprietary electro-optic grating-coupled SPR platform (EOSPR) would investigate changes in bound mass at as many as 100,000 regions of interest simultaneously. The sensitivity increase over current instrumentation is expected to improve over current label-free state-of-the-art in that data collection will be significantly more rapid in the proposed systm than in other high-content devices. The inclusion of additional data into the averaged measurement implies a greater signal-to-noise ratio, but further advantages are available to the EOSPR system that would not be viable in other SPR platforms. A signal-chopping scheme that could only be implemented on a system that scans as rapidly as the EOSPR device is expected to reduce the noise of the instrumentation. The combination of better signal and reduced noise is expected to lead to increases in label- free detection sensitivity that could approach that of label-based techniques. In addition, since scans of the SPR curves could be completed much more rapidly than in classic devices, the direct measure of more rapid binding events becomes possible. The steps that will be required to verify if this technology can be turned into a commercial product include: modeling of the proposed chip, fabrication the chip, modifying an existing SPR instrument that was previously designed by Ciencia, and conducting proof-of-concept experiments on the prototype system. The objectives to meet these tasks are outlined within the body of this proposal, and strategic consulting arrangements and subcontracts will be employed to maximize the possibility of success for this potentially high-impact project. PUBLIC HEALTH RELEVANCE: Current trends in biomedical research imply that the future of medicine will rely upon ever-increasing degrees of personalized therapy. As the number of understood disease states and therapeutic options increase, so does the amount of diagnostic information necessary to make an informed decision. The proposed EOSPR technology aims to aid systems biology researchers in elucidating and understanding these complex molecular mechanisms by filling the need for a sensitive, label-free, and high-content assay that is affordable enough for widespread adoption.