The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the development of a robust capillary electrophoresis instrument with mass spectrometry detection for biomedical research, biopharmaceutical development, clinical diagnostics, and system biology. Capillary electrophoresis (CE) is a powerful liquid separation technology with remarkable potentials for bioanalysis. It was the workhorse tool for the completion of human genome project that, in part, led to the DNA sequencing market. A CE system with both optical and mass spectrometry detection will enable a deeper understanding of molecular dynamics governing biochemical processes, such as protein expression, deregulation, and interaction with other biochemical species, which could lead to breakthroughs in drug development, early diagnosis, and treatments for deadly human diseases such as cancer, diabetics, and neurodegenerative disorders. The proposed technology will offer benefits to biopharmaceutical drug development companies by increasing the efficiency of product characterization for quality improvement. It also will allow efficient routine proteomics analysis and other bioanalytical applications.
The intellectual merit of this SBIR Phase I project is to develop a next-generation capillary electrophoresis with electrospray ionization mass spectrometry (CE-ESI-MS) for protein characterization. CE-ESI-MS allows high efficiency separation and characterization of several biochemical species including proteins. However, leveraging the intrinsic advantages of CE-ESI-MS has been difficult due to lack of robust, easy-to-use instrumentation, which has made adoption for routine applications uncommon. This research will develop and evaluate a novel CE-ESI-MS instrument for protein characterization. The proposed instrument will employ original innovations to overcome the limitations of the incumbent technologies and exceed their capabilities. A novel fluidic nanoport for sample and buffer manipulation will be developed to allow analysis from 1 microL or less sample volume. The nanoport will employ a fully automated design with less operator intervention. This will be useful for sample-limited applications such as in clinical analysis. In addition, the instrument will utilize a hybrid electrospray ionization interface for simultaneous optical and MS detection, which no existing technology offers. Combining CE's ultrahigh efficiency with robust quantitative characteristics of optical detection and the molecular identification of mass spectrometry will be a powerful tool for bioanalysis. This combination will represent a significant advancement over the state-of-the-art and enhance the means of interrogating proteins and their biochemical functions in biological samples. The proposed innovations will significantly enhance the robustness and capabilities of CE-ESI-MS for fast, efficient, and deep bioanalysis.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
