MALDI Ion-Trap Nucleic Acid Analysis With Sensitive Fragment Detection
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Solution Overview
Problem
Existing nucleic acid structure analysis methods face challenges in detecting fragment ions with high sensitivity due to nucleic acid decomposition during ionization and the generation of alkali metal ion adducts, particularly for larger molecular weights, making it difficult to introduce sufficient precursor ions for collision-induced dissociation.
Innovation Solution
A method using an ion trap type mass spectrometer with a matrix-assisted laser desorption/ionization (MALDI) ion source for nucleic acid structure analysis, involving ionization, low-energy collision-induced dissociation within the ion trap, mass spectrometry of fragment ions, and structure determination based on mass information.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If collision-induced dissociation is used for structural analysis, then fragment ions can be generated for identification, but sufficient precursor ions cannot be introduced due to nucleic acid decomposition during ionization
Solution Approach 1:
The patent extracts and eliminates alkali metal ions from the ionization environment by using an alternative ionization method (MALDI with specific matrix) that does not generate alkali metal ion adducts, thereby preventing the loss of precursor ions and enabling sufficient introduction of intact nucleic acid molecules for subsequent fragmentation analysis
Solution Approach 2:
The patent changes the ionization parameters by switching from conventional ionization methods to MALDI with specifically selected matrices (such as 2,4,6-trihydroxyacetophenone monohydrate or 2-aminobenzoic acid), which alter the ionization mechanism to prevent alkali metal ion adduct formation while maintaining sufficient precursor ion generation
2Use of energy by moving object
If alkali metal ion adducts are generated during ionization, then ionization efficiency increases, but sensitivity of molecular weight-related ions decreases
Solution Approach 1:
The patent converts the potential harm of alkali metal ion interference into a benefit by deliberately selecting matrix compounds that contain basic groups capable of accepting protons, thereby creating a controlled ionization environment where the matrix itself serves as the proton acceptor rather than alkali metal ions, eliminating the harmful adduct formation while maintaining efficient ionization
3Productivity
If laser intensity is increased to promote ion dissociation, then in-source decay is enhanced, but nucleic acid decomposition during ionization increases
Solution Approach 1:
The patent performs preliminary action by selecting and optimizing the matrix compound before ionization, choosing matrices with specific properties (aromatic compounds with basic groups) that pre-condition the ionization environment to favor intact precursor ion formation, thereby preventing decomposition before the ion dissociation step is intentionally applied
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method enables detection of fragment ions with high sensitivity by suppressing alkali metal ion adduct generation, allowing for accurate nucleic acid structure analysis through low-energy collision-induced dissociation.
Implementation Method 1
an ionization step of ionizing a nucleic acid contained in a sample by the ion source; having an ion source performing a matrix-assisted laser desorption/ionization method
Implementation Method 2
an ion dissociation step of dissociating a protonated molecule or a deprotonated molecule of the nucleic acid generated in the ionization step by collision-induced dissociation inside an ion trap of the mass spectrometer
Data Source
AI summary
A method for nucleic acid structure analysis using an ion trap type mass spectrometer having an ion source performing MALDI includes: an ionization step of ionizing a nucleic acid contained in a sample by the ion source; an ion dissociation step of dissociating a protonated molecule or a deprotonated molecule of the nucleic acid generated in the ionization step by collision-induced dissociation inside an ion trap of the mass spectrometer to generate a plurality of fragment ions; a mass spectrometry step of performing mass spectrometry on the plurality of fragment ions generated in the ion dissociation step to acquire mass information of the plurality of fragment ions; and a structure determination step of determining at least a part of a structure of the nucleic acid based on the mass information of the plurality of fragment ions acquired in the mass spectrometry step.