SBIR Phase I: Delving Deeper into the Proteome

这项小型企业创新研究（SBIR）第一阶段项目旨在证明一种从人体体液样本中去除大量蛋白质的新方法的概念验证。如果它是成功的，提出的方法可能会改变寻找和开发新的蛋白质生物标志物。鉴定人体体液中的稀释蛋白生物标志物是困难的。可能有成千上万种独特的蛋白质，它们的浓度变化超过10个数量级。所提出的方法包括通用仪器和相关试剂，旨在执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缩放到许多数量级，这对于发现稀释的蛋白质生物标志物非常重要。最后，该方法以浓缩和纯化蛋白质为前端，为发现新的生物标志物的传统方法：2D凝胶电泳（差分凝胶电泳）和自下而上的蛋白质组学方法制备样品。该项目的更广泛影响/商业潜力是增加个性化医疗中蛋白质诊断的成功使用，这在药物开发、靶向和部署方面发挥着重要作用。人体体液样本的复杂性削弱了蛋白质组学的潜力。一旦有效的预处理方法被开发出来，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，看到更稀释的物种，这些物种可能是疾病的生物标志物。这有可能在生物标志物发现数据的基础上大幅提高蛋白质组学数据的质量。反过来，这将有助于加速新药上市，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.