The overall low ion yield and sensitivity issues due to ion suppression, using traditional MALDI, make the imaging analysis of samples sometimes very challenging. Our answer to these problems is MALDI-2. The post-ionization technique reduces ion suppression effects and improves sensitivity by orders of magnitude.
After the initial MALDI process, a second laser, sitting parallel to the sample surface, fires into the evolving plume and post-ionizes neutral (mainly matrix) molecules. A charge transfer from post-ionized matrix molecules to neutral analyte molecules leads to an amazing sensitivity gain for many analytes.
timsTOF fleX is now available with the innovative and powerful MALDI-2 technology option. This post-ionization technique leads to both a significant boost in ion yields and reduction in ion suppression effects, resulting in a signal increase of up to 1-3 orders of magnitude compared to traditional MALDI experiments. For a MALDI Imaging experiment, this increased efficiency translates to more than double the number of molecules detected per pixel resulting in much improved physiological context.
OMICS studies involving small molecules desorbed from tissues sections such as lipidomics and metabolomics typically involve biomolecules from a wide variety of chemical classes. These studies benefit from MALDI-2 as the technique provides access to many more compounds, providing unique insight into nature’s complexity. The combination of TIMS and MALDI-2 is uniquely powerful as richer ion yields from the post-ionization process produce mass spectra with higher information content. TIMS provides fast orthogonal separation that efficiently unravels these complex spectra where each m/z can contain many overlapping features. The result is not only the ability to extract information from single isobars, but also exact masses that have different ion mobilities. Collisional Cross Section (CCS) values are recorded for each one of the spectral components for comparison to databases or LC/MS results.
Bruker supplies all elements needed for performing successful MALDI-2 experiments from the necessary matrix and IntelliSlides™, to expert application support, and intuitive and user-friendly software solutions.
fleXmatrix™ for MALDI-2
A major limiting factor in modern drug development is use of the “well-stirred model” which homogenizes organs and tissues prior to analysis and quantitation with LC-MS studies. This approach is well-suited to providing exact amounts of drugs and metabolites within a target organ, but not readily compatible with pathology methods that seek to describe physiological effects of drug compounds.
MALDI Imaging has made a significant impact towards the conversion of plasma
to tissue models by pinpointing the exact location of drugs and metabolites in tissue. MALDI-2 enhances molecular imaging for pharma studies by increasing overall sensitivity enabling quantitation for a wider range of dosing levels. Additionally, the increased variety of molecular classes seen by MALDI-2 expands the applicability of imaging to many more pharma projects that involve both xenobiotics and endogenous molecules.
A study comparing detection sensitivity from MALDI and MALDI-2. Dilution series or single dilutions of different analytes such as caffeine, prednisolone, estradiol, cortisol, doxorubicin, fluoxetin, kynurenine and paclitaxel were spotted onto liver homogenate and imaged with MALDI-2 on and off. Use of MALDI-2 clearly
yields significantly higher sensitivity.
“In the last 35 years, MALDI has become a unique and rapid analytical tool for a wide variety of applications. We developed MALDI-2 to significantly extend the technique by providing much higher sensitivity for small molecules and inclusion of chemical classes that didn’t traditionally ionize. With an extensive set of unique features, the MALDI-2 empowered timsTOF fleX will take MALDI to new frontiers previously not available.“
For Research Use Only. Not for use in clinical diagnostic procedures.