Compositions and processes for improved mass spectrometry analysis
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Publication Number
US-12077819-B2
Publication Date
2024-09-03
Expiration Date
Abstract
The invention provides a novel additive for improved analysis by mass spectrometry. More specifically, ascorbic acid has been found to reduce or eliminate the presence of adducts commonly present in mass spectra. The improved processes and compositions of the invention allow for increased accuracy, sensitivity and throughput for samples analyzed by mass spectrometry.
Core Innovation
The invention relates to using ascorbic acid, or a salt, tautomer or analog thereof, as an adduct-reducing additive in mass spectrometry, including matrix-assisted laser desorption/ionization mass spectrometry. The disclosed approach suppresses ammonia adducts and sodium adducts formed during ionization and/or sample preparation.
A key aspect is a specified molar ratio of the adduct-reducing additive to the matrix material. The document describes substrate configurations in which more than one target site includes the matrix material together with the adduct-reducing additive, and it further describes options for where the additive is present, including adding the additive to an analyte, adding the additive to a matrix, or depositing an ascorbic-acid-containing matrix or substrate.
The document further describes application coverage to nucleic acids and other analytes, and it includes multiple mass spectrometry formats such as MALDI and electrospray and other formats. Reported results include reduced adduct formation, improved spectral accuracy, improved sensitivity, and improved throughput.
Claims Coverage
The independent claim coverage centers on a substrate for mass spectrometry that uses MALDI matrix target sites together with an adduct-reducing additive comprising ascorbic acid, or a salt, tautomer or analog, at a specified molar ratio. One independent claim is provided in the supplied claim list.
Target sites with MALDI matrix and ascorbic-acid adduct-reducing additive at a defined molar ratio
A substrate for mass spectrometry comprising target sites wherein more than one target site comprises a matrix material suitable for matrix-assisted laser desorption/ionization mass spectrometry and an adduct-reducing additive comprising ascorbic acid, or a salt, tautomer or analog thereof, wherein the molar ratio of the adduct-reducing additive to the matrix material is about 1:20, about 1:19, about 1:18, about 1:17, about 1:16, about 1:15, about 1:14, about 1:13 or about 1:12.
The inventive concept is captured by the substrate structure that combines MALDI matrix target sites with an ascorbic-acid adduct-reducing additive at specific molar ratios, with dependent claims refining this arrangement using narrower ratios, concentration ranges, specified matrix materials, and material property distinctions between the substrate and target sites.
Stated Advantages
Suppress ammonia and sodium adducts formed during ionization and/or sample preparation.
Improve spectral accuracy.
Improve sensitivity.
Improve throughput.
Reduce false-positive calls.
Improve call counts.
Reduce adduct formation scores for unwanted adduct peaks.
Documented Applications
Mass spectrometry analysis using MALDI, including MALDI-TOF, for samples where ammonia and sodium adducts are suppressed.
Mass spectrometry analysis using electrospray and other mass spectrometry formats in which adduct suppression is applied.
Analysis of nucleic acids, including oligonucleotides and polynucleotides, using the described adduct-reducing additive and substrate/matrix approaches.
Analysis using MALDI substrate or target-site concepts where more than one target site includes a MALDI matrix and ascorbic-acid-containing adduct-reducing additive.
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