Dual Online Liquid Chromatography Column Switching for Continuous LC-MS
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Solution Overview
Problem
Existing dual online liquid chromatography devices require significant dead time for column equilibration and sample injection, leading to inefficiencies in LC-MS experiments, particularly when using small inner diameter capillary columns with hydrophobic media, and fail to allow independent operation of two sample separation columns.
Innovation Solution
A mutually independent dual online liquid chromatography device with separate pumps, valves, and column connections enables simultaneous sample analysis in one column while equilibrating and injecting in the other, using a sample inlet valve, column selection valve, and independent column valves to allow for continuous operation and minimize dead time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If one valve is used to connect two sample separation columns, then device complexity is reduced, but the two columns cannot operate independently causing loss of time during valve switching and column equilibration
Solution Approach 1:
The patent divides the single valve system into multiple independent valves (first column valve and second column valve), allowing each sample separation column to be controlled separately. This segmentation enables independent operation of the columns, eliminating the need for valve switching between columns and reducing dead time.
Solution Approach 2:
The patent introduces a column selection valve as an intermediary component that directs the mobile phase to the appropriate column. This mediator enables smooth transitions between columns without requiring complete system shutdown or lengthy equilibration periods, resolving the time loss issue.
2Manufacturing precision
If a long sample separation column is used to improve separation efficiency, then manufacturing precision and separation performance are improved, but mass signal dead time increases as peptides travel longer distance
Solution Approach 1:
The patent implements continuous analysis by having one column in analysis mode while the other is in equilibration mode. This continuity eliminates idle time in the mass spectrometer, as a column is always ready to provide peptide signals, thereby reducing mass signal dead time while maintaining long column length for high separation efficiency.
Solution Approach 2:
The patent performs preliminary equilibration of the second column while the first column is conducting analysis. This preliminary preparation ensures that the second column is ready for immediate analysis without requiring the mass spectrometer to wait, thus reducing dead time while maintaining optimal separation conditions.
3Measurement precision
If small inner diameter capillary columns with hydrophobic media are used to improve sensitivity, then measurement precision is improved, but column equilibration time increases significantly
Solution Approach 1:
The patent implements periodic switching between two columns, where one column undergoes equilibration while the other performs analysis. This periodic alternation allows the system to maintain high sensitivity from the small inner diameter columns while reducing the effective equilibration time impact on overall experiment duration.
Solution Approach 2:
The patent performs preliminary equilibration of the standby column before it is needed for analysis. This advance preparation ensures that when the column is switched to, it is already equilibrated and ready for immediate use, eliminating the need to extend analysis time to accommodate equilibration.
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 device achieves efficient and continuous analysis by eliminating the need for column equilibration downtime, reducing mass signal dead time, and maximizing reverse phase chromatography separation space, thereby improving peptide detection and separation performance.
Implementation Method 1
when hydrophobic media are packed in capillary columns having a large length and a small inner diameter
Data Source
Figure 1
Figure 2
Figure 3~4
AI summary
Disclosed are a mutually independent dual online liquid chromatography device and a control method thereof. The mutually independent dual online liquid chromatography device according to the present disclosure includes a first pump configured to inject a first solvent or a mixed solution containing the first solvent and a second solvent; a second pump configured to inject the first solvent or the mixed solution containing the first solvent and the second solvent; a sample inlet valve to which the first pump and a sample injector configured to inject a sample are connected; a first column valve to which a first sample separation column is connected; a second column valve to which a second sample separation column is connected; and a column selection valve to which the second pump is connected, and interposed between the sample inlet valve, and the first column valve and the second column valve to inject the sample fed from the sample inlet valve onto any one of the first sample separation column and the second sample separation column to separate and analyze the sample in one sample separation column while allowing for wash and equilibration, sample injection and isocratic elution of the other sample separation column.