Nanotechnology-Enabled Targets for High-Throughput Molecular Formula Determination of Small Molecules without LC-separations using NALDI-TOF-MS

The novel FlashFormula™ solution allows for the identification and molecular sum formula determination of small molecules for use with Bruker’s FLEX™-series of laser desorption ionization (LDI) time-of-flight (TOF) mass spectrometers and processing software.  The method uses the robust and sensitive nanotechnology-based NALDI targets developed for direct deposit, matrix-free LDI analysis.

NALDI targets have significant throughput and ease-of-use benefits for the analysis of a wide variety of small molecules such as drug compounds, small peptides, natural products, pesticides, low mass polymers, as well as polymer additives such as plasticizers and stabilizers.  Many of these molecules were previously difficult to analyze with MALDI-TOF mass spectrometers and are typically analyzed with LC-MS (liquid chromatography – mass spectrometry), which is time-consuming, less robust and requires more operator training.

Bruker’s SmartFormula™ method uses a True Isotopic Pattern (TIP) fitting algorithm plus accurate mass information for obtaining molecular sum formulae with ESI-TOF and FTMS instruments. Now the same approach is enabled for rapid compound identification and sum formula determination from NALDI-TOF results. For small molecules, the accurate isotopic pattern measured with the FLEX instruments, together with LDI-TOF mass accuracy in the low-ppm range using internal or near-neighbour calibration, often enables unique formula determination.  Compounds containing elements such as halogens, sulphur, phosphorus or organometallic complexes, also typically give dependable isotopic patterns and formula results.

FlashFormula™ is a name that reflects the speed and simplicity of molecular formula finding with a NALDI-TOF system. The dedicated 96-position NALDI targets have a form-factor compatible with all FLEX -series instruments. Small molecules are captured from liquid droplets onto the targets, an optional washing step removes salts and protein contaminants, and measurement takes a few seconds per sample, followed by automated data interpretation. Detection limits are compound dependant, but many molecules give impressive results at a low picogram level on target. A linear quantitation range of more than 3 orders of magnitude is possible with the addition of known levels of an internal calibrant.

Users of FlashFormula are expected to include the many labs where the majority of research focuses on conventional MALDI-TOF analysis of proteins, peptides and polymers, but where there is additional need for small molecule analysis.  By enabling such analyses on the same analytical platform, instrumentation purchasing and training needs are greatly simplified.

For research use only. Not for use for diagnostic purposes.