Multiplexed Precursor Ion Selection in Mass Spectrometry

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Solution Overview

Problem

Conventional high throughput quantitative mass spectrometry analysis using multiple reaction monitoring (MRM) faces a tradeoff between the overall duty cycle of the data collection process and the signal-to-noise ratio (S/N) of the quantitative data, where improving one aspect adversely affects the other.

Innovation Solution

A system utilizing an electrical field potential barrier for multiplexed precursor ion selection and transmission, where a processor applies alternating current (AC) voltage frequencies to resonate and direct current (DC) voltage to transmit multiple precursor ions simultaneously, allowing for improved duty cycle without reducing signal-to-noise ratio, using an ion source, mass isolator, and processor.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the analysis time of each target precursor ion is increased to achieve a certain signal-to-noise ratio, then the signal-to-noise ratio is improved, but the overall duty cycle of the data collection process increases (worsens)

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidduty cycle
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies periodic AC voltage at specific resonant frequencies to the quadrupole rods to selectively transmit multiple precursor ions through the barrier electrode. By using periodic resonant excitation at different frequencies for different ion species, the system achieves multiplexed transmission without serial isolation, resolving the tradeoff between signal-to-noise ratio and duty cycle

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent combines multiple precursor ion transmission events into a single simultaneous operation by using a barrier electrode with multiple resonant frequency channels. Instead of isolating and transmitting ions sequentially, the system merges multiple ion species into one multiplexed transmission event, improving duty cycle while maintaining signal-to-noise ratio

Inventive Principle:
Principle #5Merging (Combining)

2Duration of action of moving object

If the analysis time of each target precursor ion is decreased to collect quantitative data across a narrow liquid chromatography peak, then the data collection across narrow peaks is improved, but the signal-to-noise ratio of the quantitative data is reduced

Engineering Contradiction:
Improveanalysis timeVSAvoidsignal-to-noise ratio
Core Design Contradiction:
Duration of action of moving objectVSMeasurement precision

Solution Approach 1:

The system uses periodic resonant excitation at multiple frequencies simultaneously to transmit multiple precursor ions through the barrier electrode. This periodic action at resonant frequencies enables rapid sequential transmission of different ion species without requiring extended analysis time for each ion, maintaining signal-to-noise ratio while reducing overall analysis time

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The barrier electrode maintains continuous operation by rapidly switching between different resonant frequencies to transmit different precursor ions. This continuous multiplexed transmission eliminates idle time between ion analysis events, allowing the system to collect data across narrow chromatography peaks without sacrificing signal-to-noise ratio

Inventive Principle:
Principle #20Continuity of useful action

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 simultaneous selection and transmission of multiple precursor ions without compromising the signal-to-noise ratio, thereby optimizing the duty cycle of the data collection process.

Implementation Method 1

applying a direct current (DC) voltage to the barrier electrode lens relative to the rods of the selection region and rods of the transmission region in order to create an electric field potential barrier

Methodology Applied
Scientific EffectElectric field: Electric Field

Implementation Method 2

applying two or more different alternating current (AC) voltage frequencies to the rods of the selection region in order to resonate the two or more different precursor ions from the beam of ions

Methodology Applied
Scientific EffectResonance: Resonance

Data Source

PatentUS10256083B2Multiplexed precursor isolation for mass spectrometry
Publication Date: 2019.04.09 DH TECH DEVMENT PTE
  • US10256083B2 patent drawing
  • US10256083B2 patent drawing
  • US10256083B2 patent drawing

AI summary

Systems and methods for identifying precursor ions of product ions from combined product ion spectra are provided. N precursor ions are selected. N groups of the N precursor ions are created. The tandem mass spectrometer is instructed to perform multiplexed precursor ion selection on the continuous beam of ions, fragment each of the N−1 precursor ions, and measure the intensities of the product ions, producing N product ion spectra. A heat map is plotted, producing N heat maps. The N product ion spectra are combined into a combined product ion spectrum. A corresponding precursor ion of a peak is identified by finding a heat map of the N heat maps that does not have data for the mass of the peak and determining that a precursor ion of the N precursor ions that is not included in a group that produced the heat map is the corresponding precursor ion.