Matrix-assisted laser desorption/ionization mass spectrometry method
Inventors
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Assignees
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BioneerBioneer is a biotechnology company specializing in molecular biology, offering solutions in nucleic acid synthesis, molecular diagnostics, protein production, and laboratory automation. The company's expertise covers oligonucleotide chemistry, gene synthesis, sample preparation, molecular diagnostics, and analytical services such as mass spectrometry and sequencing, serving clinical, research, and industrial sectors globally.
Bioneer is a biotechnology company specializing in molecular biology, offering solutions in nucleic acid synthesis, molecular diagnostics, protein production, and laboratory automation. The company's expertise covers oligonucleotide chemistry, gene synthesis, sample preparation, molecular diagnostics, and analytical services such as mass spectrometry and sequencing, serving clinical, research, and industrial sectors globally.
Publication Number
US-11545349-B2
Publication Date
2023-01-03
Expiration Date
Abstract
The present invention relates to a matrix-assisted laser desorption ionization mass spectrometry method and, specifically, a mass spectrometry method according to the present invention comprises the steps of: acquiring a mass spectrum of an analyte by performing matrix-assisted laser desorption ionization of the analyte, wherein a detection spectrum, which is the mass spectrum of the analyte, is acquired using each of two or more matrixes different from one another; and removing, from each detection spectrum, a peak of a corresponding matrix to obtain a matrix-removed spectrum, and then acquiring a corrected mass spectrum of the analyte on the basis of a matrix-removed spectrum for each of different matrixes.
Core Innovation
The invention relates to a matrix-assisted laser desorption ionization (MALDI) mass spectrometry method for an analyte that provides detection spectra using each of two or more different matrices used for a same mass range. For each matrix, a detection spectrum consisting of peaks from the same mass ranges is obtained, and a corresponding matrix peak is removed from each detection spectrum to obtain a matrix-removed spectrum.
The method then obtains a corrected mass spectrum of the analyte on a basis of the matrix-removed spectrum of each different matrix. The corrected mass spectrum is calculated by merging peaks commonly present in the two or more matrix-removed spectrums and a peak present only in one matrix-removed spectrum.
The approach is described as applicable to low-molecular-weight analytes, including analyte molecular mass constraints such as 1000 daltons or less. Embodiments further specify matrix sets used for the same mass range, including organic matrices selected from CHCA, DHB, HABA, MBT, and 3-HPA, with an m/z separation requirement for adjacent matrix peaks.
In further embodiments, a corrected mass spectrum is formed by merging common peaks and complementary peaks, including optional intensity-correction using intensity ratios between common peaks across matrix-removed spectrums.
Claims Coverage
The independent claim covers a MALDI mass spectrometry method with 3 inventive features: obtaining detection spectra for the same mass range using two or more different matrices, removing corresponding matrix peaks to form matrix-removed spectra, and calculating a corrected mass spectrum by merging common peaks and peaks present only in one matrix-removed spectrum. Dependent claim refinements add constraints and additional rules for the merging and operational settings, including analyte molecular-mass limits, matrix selection, mass analyzer types, m/z separation, and intensity ratio correction.
Matrix-removed spectra from two or more matrices for the same mass range
A MALDI mass spectrometry method performing matrix-assisted laser desorption ionization on an analyte to obtain a mass spectrum, where a detection spectrum of the analyte is obtained using each of two or more different matrices used for a same mass range, wherein each of two or more detection spectrums consists of peaks from the same mass ranges; removing a peak of a corresponding matrix from each detection spectrum to obtain a matrix-removed spectrum.
Corrected mass spectrum calculated by merging common and complementary peaks
A MALDI mass spectrometry method subsequently obtaining a corrected mass spectrum of the analyte on a basis of the matrix-removed spectrum of each of the different matrices, wherein the corrected mass spectrum is calculated by merging peaks commonly present in the two or more matrix-removed spectrums and a peak present only in one matrix-removed spectrum.
Selected matrices from CHCA, DHB, HABA, MBT, and 3-HPA
The method where the two or more different matrices are selected from CHCA, DHB, HABA, MBT, and 3-HPA.
Analyte molecular mass of 1000 daltons or less
The method where the analyte comprises a compound with a molecular mass of 1000 daltons or less.
Mass spectrometer selected from TOF, IT, FT-ICR, quadrupole, or orbitrap
The method where a mass spectrometer is selected from TOF, ion trap (IT), FT-ICR, quadrupole, or orbitrap.
Smallest m/z difference between peaks from different matrices is at least 1
The method where the smallest m/z difference between peaks from two different matrices is at least 1.
Intensity ratio correction for complementary peaks during merging
The method where a complementary peak during merging is corrected in intensity by using an intensity ratio between the common peak of the first matrix-removed spectrum and the common peak of the second matrix-removed spectrum.
Overall, the claims focus on removing matrix-origin peaks from detection spectra acquired with multiple different matrices over the same mass range, and then computing a corrected analyte mass spectrum by merging peaks that are common across matrices and peaks present only in one matrix-removed spectrum, with dependent refinements covering specific matrices, analyte molecular-mass limits, mass analyzer types, an m/z separation constraint, and optional intensity ratio correction for complementary peaks.
Stated Advantages
Reduces matrix interference by removing matrix peaks from each detection spectrum and forming a corrected mass spectrum based on matrix-removed spectra.
Documented Applications
Improved recovery of biomarker and isotope-labeled amino acid spectra by using multiple matrices and merging intensity-corrected complementary peaks.
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