Nanotechnology-enabled targets for high-throughput molecular formula determination of small molecules without LC-separations using Naldi-Tof-MS
At Pittcon 2008, Bruker Daltonics announced FlashFormula, for the identification and molecular sum formula determination of small molecules for use with Bruker's Flex-series of laser desorption ionisation (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 plasticisers and stabilisers.
Many of these molecules were previously difficult to analyse with Maldi-Tof mass spectrometers and are typically analysed 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 three 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.
Catherine Stacey, Bruker Daltonics US director of applications, commented: "The unique capabilities for fast and easy identification and formula determination without lengthy LC separations offered by FlashFormula, using Naldi targets in combination with our industry-leading Tof and Tof/Tof mass spectrometers, open up a breadth of new research and applied market opportunities for small molecules analysis".
"We are very pleased to offer this enabling nanotechnology-based solution to address new application areas."
