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

描述(由申请人提供)：这项第一阶段SBIR提案的目标是开发一种基于表面等离子体共振(SPR)的新型仪器平台，如果得到验证，将极大地提高这项无标记技术的实用性，使研究人员在系统生物学研究中利用高含量分析。该平台的好处来自于检测范式的改变，允许固态测量SPR移位作为电压的函数。通过改变角度扫描或波长扫描的方法，拟议的专有电光光栅耦合SPR平台(EOSPR)将同时调查多达10万个感兴趣区域的束缚质量变化。与当前仪器相比，灵敏度的提高有望改善当前无标签的最先进水平，因为在拟议的系统中，数据收集将明显比在其他高内容设备中更快。将更多数据包含在平均测量中意味着更高的信噪比，但EOSPR系统具有在其他SPR平台上不可行的进一步优势。信号斩波方案只能在扫描速度与EOSPR设备一样快的系统上实施，预计将降低仪器的噪音。更好的信号和更低的噪声的结合有望导致无标记检测灵敏度的提高，这可能接近基于标记的技术。此外，由于SPR曲线的扫描可以比传统设备更快地完成，因此直接测量更快速的结合事件成为可能。验证这项技术是否可以转化为商业产品所需的步骤包括：对拟议的芯片进行建模，制造芯片，修改Ciencia之前设计的现有SPR仪器，以及在原型系统上进行概念验证实验。本提案正文概述了实现这些任务的目标，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可能产生重大影响的项目取得成功的可能性。 公共卫生相关性：目前生物医学研究的趋势表明，医学的未来将依赖于不断增加的个性化治疗程度。随着了解的疾病状态和治疗选择的数量增加，做出知情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、无标记和高含量分析的需求，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，并且足够负担得起，以便广泛采用。

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.