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.
