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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 建立在亲和力传感基础上的生物医学分析在免疫分析、基因图谱、转录因子研究和药物发现方面取得了巨大的成功。然而，亲和力分析有一个致命弱点，即积极的信号完全依赖于探针-靶相互作用的设计、工程和事先验证。这将亲和力分析限制在目标先验已知的生物传感子集上， 目标是测量样本中的目标量以进行检测、诊断或 心理治疗。发现，特别是生物标记物的发现，亲和阵列是不可能的，因此高通量、无标记、高灵敏度的技术进步还没有被广泛应用于发现。我们正在进行SEED项目，以开发将波士顿大学开发的光谱反射生物传感(SRB)的量化、高通量无标记微阵列平台与质谱学相结合的技术，以展示量化、高通量的生物标记物发现。在技术开发过程中，我们希望为现有应用设计和优化直接验证SRB系统的协议，并随着技术的评估和优化开发新的应用。最初的MALDI-TOF MS分析似乎很有希望。已经获得了大学内部资金，以支持这项工作的初始阶段。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 seed 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.