SBIR Phase I: Delving Deeper into the Proteome

这个小型企业创新研究（SBIR）第一阶段项目旨在证明一种从人体液体样本中去除丰富蛋白质的新方法的概念验证。 如果成功，该方法可能会改变新蛋白质生物标志物的搜索和开发。 鉴定人体体液中稀释的蛋白质生物标志物是困难的。 可能有数十万种独特的蛋白质，其浓度变化超过10个数量级。 所提出的方法包括通用仪器和相关试剂，旨在进行样品预处理步骤，以去除丰富的蛋白质，同时保留稀释的蛋白质，从而压缩样品的动态范围。 它可以从今天常规使用的样品体积扩展到更大的许多数量级，这对于发现稀释的蛋白质生物标志物很重要。 最后，该方法浓缩和纯化蛋白质作为前端，为用于发现新生物标志物的传统方法制备样品：2D凝胶电泳（差异凝胶电泳）和自下而上的蛋白质组学方法。 该项目更广泛的影响/商业潜力是增加蛋白质诊断在个性化医疗中的成功使用，这在药物开发，靶向和部署中发挥着重要作用。 蛋白质组学的潜在力量被人体体液样本的复杂性冲淡了。 一旦开发出有效的预处理方法，选择性地去除丰富的蛋白质，人们就可以更深入地研究蛋白质组，以看到可能是疾病生物标志物的更稀的种类。 这有可能大大提高生物标志物发现数据依赖的蛋白质组学数据的质量。 反过来，这将有助于加快新药上市，针对适当的临床人群，并有助于监测疾病进展。 这些都可能对个性化医疗和公共卫生产生深远的影响。

This Small Business Innovation Research (SBIR) Phase I project seeks to demonstrate proof-of-concept for a new method that removes abundant proteins from human fluid samples. If it is successful, the proposed method potentially could transform the search for and development of new protein biomarkers. Identifying dilute protein biomarkers in human fluids is difficult. There can be hundreds of thousands of unique proteins that can vary in concentration over 10 orders of magnitude. The proposed method, comprising a general-purpose instrument and allied reagents, is intended to perform sample pretreatment steps to remove abundant proteins while retaining dilute proteins, and thereby compress the dynamic range of the sample. It can be scaled from sample volumes used routinely today, to many orders of magnitude larger, which is important to uncover dilute protein biomarkers. Finally, the method concentrates and purifies proteins as a front end to prepare samples for the traditional methods used to discover new biomarkers: 2D gel electrophoresis (Difference Gel Electrophoresis) and bottom-up proteomics methods. The broader impact/commercial potential of this project is to increase the successful use of protein diagnostics in personalized medicine, which is assuming a major role in drug development, targeting and deployment. The potential power of proteomics is diluted by the complexity of human fluid samples. Once effective pretreatment methods are developed that remove abundant proteins selectively, one can delve more deeply into the proteome to see the more dilute species which may be disease biomarkers. This has the potential to increase substantially the quality of proteomics data upon biomarker discovery data rely. In turn, this will help to speed new pharmaceuticals to the market, target proper clinical populations, and help to monitor disease progression. These all may have a profound effect on personalized medicine and public health.