MS3 CID Event Segmentation for Cycle Time Reduction

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Solution Overview

Problem

MS3 experiments on ion trap mass spectrometers face long cycle times due to the time required for handling collision gas during CID events and the lack of tools to optimize the final fragmentation stage, particularly in full-scan MS3 experiments.

Innovation Solution

The CID event is divided into two time periods, allowing the pulse valve to open and close during the event to overlap pump-down time with fragmentation, and using different CID voltages to enhance fragmentation efficiency, while also optimizing the secondary fragmentation stage by selecting appropriate second-generation fragment ions based on intensity and signal-to-noise ratio.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If a single CID event with simultaneous collision gas pulse and CID voltage application is used, then the fragmentation process is simple, but the cycle time is long due to the required pump down period

Engineering Contradiction:
ImproveCID event cycle timeVSAvoidCID event structure
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The CID event is divided into two sequential sub-events: a first CID event that applies CID voltage without collision gas, and a second CID event that applies both CID voltage and collision gas pulse. This segmentation allows the pump down period to overlap with the first CID event, thereby reducing the total cycle time while maintaining effective fragmentation through the second CID event.

Inventive Principle:
Principle #1Segmentation

2Reliability

If collision gas is pulsed during CID event, then fragmentation efficiency is improved, but pump down time is required which extends the overall cycle time

Engineering Contradiction:
Improvefragmentation efficiencyVSAvoidpump down time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The first CID event is performed as a preliminary action before the collision gas pulse is introduced. This initial CID event begins the fragmentation process and can proceed simultaneously with the pump down of excess collision gas from the previous event, thereby preparing the system for the main fragmentation event while minimizing idle time.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The CID process uses periodic action by alternating between two types of CID events: one without collision gas and one with collision gas pulse. This periodic structure allows the system to rhythmically perform fragmentation while managing collision gas levels, ensuring that pump down time does not extend the overall cycle by overlapping it with the first CID event of each period.

Inventive Principle:
Principle #19Periodic action

3Measurement precision

If conventional single-stage fragmentation is used, then the process is straightforward, but specificity is limited and chemical noise interference occurs

Engineering Contradiction:
ImprovespecificityVSAvoidfragmentation stages
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The fragmentation process is segmented into two distinct stages: a first CID event that produces initial fragment ions, and a second CID event that further fragments selected ions with collision gas. This two-stage segmentation enhances specificity by enabling sequential filtering of ions based on mass-to-charge ratio, thereby reducing chemical noise interference while maintaining manageable system complexity.

Inventive Principle:
Principle #1Segmentation

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 reduces the overall time of the CID event and increases the generality of fragmentation, improving the throughput and specificity of MS3 experiments by efficiently managing collision gas and optimizing fragmentation conditions.

Implementation Method 1

an ion trap mass spectrometer uses collision-induced dissociation (CID) for the fragmentation events in MS3 experiments

Methodology Applied
Scientific EffectCollision-induced dissociation:

Implementation Method 2

the pulse of collision gas normally requires a 'pump down' period to get rid of excess collision gas and avoid over pressuring the system

Methodology Applied
Scientific EffectPumping: Pump

Data Source

PatentUS9768002B2Parsing events during MS3 experiments
Publication Date: 2017.09.19 DH TECH DEVMENT PTE
  • US9768002B2 patent drawing
  • US9768002B2 patent drawing
  • US9768002B2 patent drawing

AI summary

Systems and methods are provided for reducing the time period of a CID event of an MS3 experiment and making the overall fragmentation event more generic. A CID event of an MS3 experiment performed on a sample by a mass spectrometer is divided into two time periods using a processor. At the beginning of a first time period of the CID event, the mass spectrometer is instructed to both open a pulse valve in order to pulse a collision gas and apply a first CID voltage. At the beginning of a second time period of the CID event, the mass spectrometer is instructed to both close the pulse valve and apply a second CID voltage. The mass spectrometer is pumped down during the second time period. The overlap in time of the pump down and CID reduces the overall time period of the CID event.