SBIR Phase I: NIMS: A Matrix-Free Mass Spectrometry Imaging Platform for High Sensitivity, Spatial Resolution and Throughput

This Small Business Innovation Research (SBIR) Phase I project proposes the development of a new imaging platform based on mass spectrometry that addresses the need for a technology with high spatial resolution and sensitivity in the low-mass range. Mass spectrometry imaging (MSI) is a rapidly growing area because it does not require a labeled sample, offers location-specific chemical information, and has high information content with potentially thousands of compounds detected at each pixel in the image. However, broad-based applicability of MSI has not been realized due to limited spatial resolution and sensitivity in the low-mass range. The overall Phase I goal is to overcome the current MSI limitations and expand the applicability by utilizing nanostructured surfaces that take advantage of an entirely different desorption/ionization mechanism than current surface-based mass analysis technologies. Our Phase I objective is to develop two prototypes based on this nanostructured surface. First, we will develop a prototype for mass-based imaging with high spatial resolution and high low-mass sensitivity that can be used for tissue imaging. Second, we will produce a prototype that enables a new approach to high-throughput screening of enzymatic activity libraries based on mass imaging, with a projected throughput of more than 10,000 assays/day. The broader impact/commercial potential of this project is that mass-based imaging can be used in applications that are difficult or impossible with the current MSI technologies, which includes the matrix-assisted laser desorption/ionization (MALDI) and secondary-ion mass spectrometry (SIMS) technologies. The ability to perform MSI in the low-mass range will have particularly high impact because many important classes of molecules fall within this range including biofuels, therapeutic compounds, disease-relevant metabolites, environmental toxins, food contaminants, and industrial compounds. Societal and commercially important mass-based imaging applications of the proposed platform include 1) animal/plant tissue imaging for drug discovery, drug localization/metabolism, disease marker discovery, environmental studies and 2) biofilm imaging for biofuel production and environmental remediation. The proposed MSI-based high-throughput screening platform has significant potential for discovery of new enzymes for biofuel production industrial processes as well as therapeutic enzyme inhibitors. In addition, the nanostructured surfaces used in this proposal have a low barrier of entry and high value to the customer because the end user can take advantage of the new capabilities enabled by the proposed platform, while using the same commercially available laser desorption/ionization mass spectrometer that they currently use for matrix-assisted laser/desorption ionization (MALDI).