Serial LC Columns for Multi-Eluant Mass Spectrometry
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Solution Overview
Problem
Current LC/MS/MS analysis methods require multiple runs under different conditions to separate target components from impurities, leading to reduced throughput and reproducibility issues, especially when analyzing samples with a wide variety of chemical or physical properties.
Innovation Solution
A method involving serially connected columns with different packing materials and eluants, allowing for multiple LC separations with distinct separation characteristics in a single analysis, including a sample injection step, a first analysis step with a first eluant, and a second analysis step with a second eluant differing in composition, to effectively separate target components from each other and impurities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple LC/MS/MS analyses are performed under different LC conditions to separate target components from impurities, then the separation quality and analysis accuracy are improved, but the analysis throughput is reduced and reproducibility deteriorates
Solution Approach 1:
The patent merges multiple LC separation processes with different separation characteristics into a single integrated system. By connecting multiple LC columns (e.g., C18 column and HILIC column) in series or parallel configuration, the system can perform multiple separations simultaneously or sequentially within one LC/MS/MS run, thereby maintaining high analysis accuracy while improving throughput
Solution Approach 2:
The patent creates a universal LC system that can handle diverse target components with varying chemical and physical properties through a single multi-functional column configuration. The system uses columns with different packing materials (reversed phase, normal phase, HILIC) to provide multiple separation mechanisms in one apparatus, enabling it to analyze various compound types without requiring multiple separate instruments
2Manufacturing precision
If multiple LC/MS/MS analyses are performed under different LC conditions to separate target components from impurities, then the separation quality is improved, but the time consumption increases
Solution Approach 1:
The patent implements continuous separation action by configuring multiple LC columns to operate in a coordinated manner. While one column is separating early-eluting components, another column simultaneously separates late-eluting components, ensuring that the useful separation action continues without interruption throughout the analysis period, thereby reducing total analysis time while maintaining high separation quality
Solution Approach 2:
The patent adds a temporal dimension to the separation process by using columns with different separation characteristics that elute components at different times. This multi-dimensional approach (combining spatial separation in multiple columns with temporal separation through different elution profiles) allows comprehensive separation of diverse components within a single time frame
3Manufacturing precision
If multiple LC/MS/MS analyses are performed under different LC conditions to separate target components from impurities, then the separation quality is improved, but the data consistency deteriorates
Solution Approach 1:
The patent merges multiple separation processes into a single integrated LC system with unified control and data acquisition. By performing all separations through one instrument with consistent MS/MS detection conditions, the system ensures that all data are acquired under the same detection parameters, thereby maintaining high data consistency and reliability across all analyzed components
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
This approach enables highly reproducible mass spectrometric analysis with reduced ion suppression or enhancement, allowing for the analysis of a considerable number of target components with varying characteristics in a single LC/MS or LC/MS/MS analysis, improving throughput and data consistency.
Implementation Method 1
a plurality of columns which are configured to be serially connectable to each other and are respectively packed with different kinds of packing materials
Implementation Method 2
liquid chromatograph mass spectrometry (LC/MS analysis or LC/MS/MS analysis)
Implementation Method 3
a suppression of the ionization of a target component ('ion suppression') or promotion of the ionization ('ion enhancement') may occur in the mass spectrometry (MS)
Data Source
AI summary
In an LC/MS/MS analysis: injecting a sample into a passage leading to a column group provided in a liquid chromatograph, the column group including a plurality of columns serially connected to each other and packed with different kinds of packing materials; supplying an eluant to one or a plurality of columns including a column located most downstream, to separate a portion of the target components in the sample in the one or plurality of columns, and sequentially elute those components from the most downstream column to perform mass spectrometry; and supplying a different eluant to one or a plurality of columns including the most downstream column, to separate at least a portion of the target components which stayed uneluted in the one or plurality of columns in the first analysis step, and sequentially elute those components from the most downstream column to perform mass spectrometry.