National Science Foundation
IIBR Instrumentation: Sub-micrometer Resolution Mass Spectrometry Imaging by Deep-UV Laser Ablation and Post-ionization
- DBI:1951447
- $836,650
- Role: PI
- 4/2020-3/2024
Abstract
An award is made to Louisiana State University and Baylor University to develop an instrument for imaging biomolecules in tissue that uses mass spectrometry and has both high spatial resolution and high mass range. The instrument is simple, low-cost, and easy to use and will bring high-performance untargeted biochemical imaging to a broad range of researchers in fundamental and translational biological research. This instrument will be used in a combined sampling and imaging workflow with the ability to localize, identify, and quantify biomolecules in tissue. Mass spectrometry has the unique advantage among in vitro imaging methods in that it is un-targeted; thus, it has the capability of detecting lipids, metabolites, peptides and proteins without prior information about the components. This instrument addresses a critical technological barrier of large biomolecule ionization at submicrometer precision that is necessary for cellular localization of compounds. The user community benefiting from the proposed instrument includes researchers in fundamental and applied areas that require spatially localized chemical compound identification and quantification. Basic biological research will benefit from an instrument that can analyze a wide range of biochemical classes. Translational research will benefit from an instrument that is robust and highly sensitive and the relatively low cost and ease of use will bring it to research centers where this capability is not typically found. The mass spectrometry imaging project will leverage STEM education resources for high-school, undergraduate, graduate, and postdoctoral education and training. The project will provide research opportunities for students participating in the NSF S-STEM Scholars program and the Louis Stokes Louisiana Alliance for Minority Participation. Opportunities will be available for undergraduate researchers from the State participating in the Louisiana Biomedical Research Network summer research program and for local middle and high school science teachers through the LSU Cain Center for STEM Literacy.
Current mass spectrometry imaging techniques require a compromise between secondary ion mass spectrometry (SIMS) that uses a precisely focused beam of ions to image small molecules and matrix-assisted laser desorption ionization (MALDI) that uses a less-focused but gentler laser beam to image large molecules. The proposed research eliminates the need for this spatial resolution and mass range compromise through the use of a highly focused deep-UV ablation laser combined with an ultraviolet post-ionization laser for two-laser MALDI (MALDI-2). The approach uses the MALDI effect on ablated tissue and matrix material and therefore has the mass range and gentle ionization properties of MALDI. Furthermore, it uses simple, robust, and relatively low-cost mass spectrometry technology that has the potential to bring the capabilities of the instrument to more biological imaging researchers. MALDI-2 imaging is combined with deep-UV laser ablation sampling for liquid chromatography tandem mass spectrometry analysis. The results of the project will be disseminated using a variety of social media platforms as well as traditional methods of publications and conference presentations An online presence will be established through a dedicated website and social media that will post photos, videos, and updates on the instrument. The website will be mobile device compatible and feature photos and videos of the instrument in operation as well as the data obtained. The site will also include instructions and protocols, example data, and instrument control and analysis software. The anticipated outcome of this project is a prototype deep-UV ablation MALDI-2 imaging mass spectrometer with 1 µm spatial resolution and greater than 10,000 Da mass range. The instrument will be capable of imaging with the speed, ease of sample preparation, and ease of data acquisition that is comparable to conventional MALDI imaging mass spectrometry.