QUANTIFIED HIGH-THROUGHPUT BIOMARKER DISCOVERY BY MS ON LABEL-FREE ARRAYS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 围绕亲和传感构建的生物医学检测在免疫检测、基因分析、转录因子研究和药物发现方面取得了巨大成功。然而，亲和力测定有一个致命弱点，  阳性信号完全依赖于探针-靶相互作用的设计、工程和预先验证。这将亲和测定限制于其中靶是先验已知的生物传感的子集， 目标是测量样品中目标的量，用于检测、诊断或 疗法发现，特别是生物标志物的发现，是不可能的亲和阵列，所以高通量，无标记，高灵敏度的技术进步还没有广泛应用于发现。我们正在开展一项新的项目，开发将BU开发的光谱反射生物传感（SRB）的定量，高通量无标记微阵列平台与质谱法相结合的技术，以证明定量，高通量生物标志物的发现。在该技术的发展过程中，我们希望设计和优化协议，直接验证SRB系统的现有应用程序，并开发新的应用程序，作为该技术的评估和优化。初步MALDI-TOF MS分析似乎很有希望。已获得大学内部资金，以支持初步阶段的工作。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Biomedical assays built around affinity sensing have achieved great success in immunoassays, gene-profiling, transcription factor studies and drug discovery. Yet affinity assays have an Achilles' heel  positive signal relies entirely on the design, engineering, and prior verification of the probe-target interaction. This restricts affinity assays to a subset of biosensing where the target is known a priori, with the goal to measure the amount of target in the sample for detection, diagnosis, or therapy. Discovery, especially biomarker discovery, is not possible with affinity arrays, so the technological advancements of high throughput, label-free, and high sensitivity have not been widely applied to discovery. We are working on a novel project to develop the technology to couple the quantified, high-throughput label-free microarray platform of Spectral Reflectance Biosensing (SRB) developed at BU to mass spectrometry to demonstrate quantified, high-throughput biomarker discovery. During the development of the technique, we expect to design and optimize protocols for direct verification of the SRB system for existing applications and to develop new applications as the technology is evaluated and optimized. Initial MALDI-TOF MS analyses seem promising. Internal university funding has been obtained to support the initial stages of the work.