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

描述（由申请人提供）：本阶段I SBIR提案的目的是开发一种基于表面等离子体共振（SPR）的新型仪器平台，如果经过验证，将大大增加这种无标记技术在系统生物学研究中使用高含量测定的研究人员的实用性。这个平台的好处来自于检测范式的变化，允许固态测量SPR位移作为电压的函数。通过远离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个感兴趣区域的结合质量变化。与目前的无标签最先进的仪器相比，灵敏度的提高预计将改善，因为在拟议的系统中，数据收集将比其他高含量设备更迅速。将额外的数据包括到平均测量中意味着更大的信噪比，但是EOSPR系统可以获得在其他SPR平台中不可行的其他优点。一个信号斩波方案，只能在一个系统，扫描一样快的EOSPR设备上实现，预计将减少仪器的噪声。预期更好的信号和降低的噪声的组合导致无标记检测灵敏度的增加，其可以接近基于标记的技术的灵敏度。此外，由于SPR曲线的扫描可以比经典设备更快地完成，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，修改先前由Cietron设计的现有SPR仪器，并在原型系统上进行概念验证实验。完成这些任务的目标在本提案的正文中概述，将采用战略咨询安排和分包合同，以尽可能扩大这一可能具有重大影响的项目的成功可能性。 公共卫生相关性：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增加的个性化治疗。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，填补了对灵敏、无标记和高含量检测的需求，这种检测方法价格合理，足以广泛采用。

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.