DMS Precursor Ion Survey Scan for DIA Efficiency

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Solution Overview

Problem

Traditional data-independent acquisition (DIA) workflows in tandem mass spectrometry are inefficient, especially for samples with limited sample volumes, due to their non-specific nature, which results in unnecessary data collection and reduced productivity.

Innovation Solution

Implementing a differential mobility spectrometry (DMS) precursor ion survey scan system that uses a processor to ionize samples, separate precursor ions with compensation voltages, and measure mass-to-charge ratios, producing a two-dimensional mapping to optimize the selection of precursor ions for fragmentation, thereby improving the efficiency of DIA workflows.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If traditional DIA workflows are used to collect data for all precursor ions in a mass range, then comprehensiveness of data collection is improved, but efficiency and productivity deteriorate due to non-specific fragmentation and unnecessary data collection

Engineering Contradiction:
Improvecomprehensiveness of data collectionVSAvoidefficiency of data collection
Core Design Contradiction:
Loss of informationVSProductivity

Solution Approach 1:

The patent performs a DMS precursor ion survey scan before the main MS/MS acquisition to identify which precursor ions are actually present in the sample. This preliminary action allows the system to select only relevant precursors for fragmentation, avoiding unnecessary data collection for absent or low-abundance ions while maintaining comprehensiveness for present ions.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system uses the two-dimensional mapping data from the DMS survey scan as feedback to dynamically adjust the MS/MS acquisition parameters. The mapping information about precursor ion distribution across CoV and m/z dimensions guides the selection of precursors for fragmentation, creating a feedback loop that optimizes both comprehensiveness and efficiency.

Inventive Principle:
Principle #23Feedback

2Productivity

If DMS precursor ion survey scan with two-dimensional mapping is implemented to optimize precursor selection, then efficiency and productivity are improved, but device complexity increases

Engineering Contradiction:
Improveefficiency of DIA workflowVSAvoidcomplexity of mass spectrometry system
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent utilizes the existing DMS device's capability to perform both ion separation and survey scanning functions. The same DMS apparatus that separates ions based on compensation voltage is used to generate the two-dimensional mapping, eliminating the need for separate specialized equipment and reducing overall system complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The two-dimensional mapping data structure serves as an intermediary that bridges the DMS survey scan and the MS/MS acquisition. This intermediate data representation simplifies the control logic by providing a clear map of precursor locations, making the complex coordination between DMS separation and MS/MS fragmentation more manageable.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Loss of information

If non-specific DIA fragmentation is performed for all precursor ions, then comprehensiveness is maintained, but sample volume requirements increase making it unsuitable for limited sample volumes

Engineering Contradiction:
Improvecompleteness of analyte coverageVSAvoidsample volume required
Core Design Contradiction:
Loss of informationVSQuantity of substance

Solution Approach 1:

The patent extracts only the necessary information from the sample by using the DMS survey scan to identify which precursor ions are actually present. Instead of fragmenting all possible precursors in a mass range, the system extracts and fragments only those precursors that are confirmed to be in the sample, reducing the total ion population that requires analysis and making the method suitable for limited sample volumes.

Inventive Principle:
Principle #2Taking out (Extraction)

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 inefficiencies in DIA workflows by selectively filtering ions and optimizing precursor ion selection, enhancing the productivity and comprehensiveness of data collection, especially for samples with limited volumes.

Implementation Method 1

an ion source configured to receive a sample and ionize the sample

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

a differential mobility spectrometry (DMS) device configured to receive ions from the ion source and to separate precursor ions received from the ion source based on a compensation voltage (CoV)

Methodology Applied
Scientific EffectDifferential mobility spectrometry: Electrophoresis

Implementation Method 3

a mass analyzer configured to receive transmitted precursor ions from the DMS device and measure the mass-to-charge ratio (m/z) intensities of the transmitted precursor ions

Methodology Applied
Scientific EffectMass analysis: Time of Flight

Data Source

PatentUS10309930B2Dynamic orthogonal analysis method
Publication Date: 2019.06.04 DH TECH DEVMENT PTE
  • US10309930B2 patent drawing
  • US10309930B2 patent drawing
  • US10309930B2 patent drawing

AI summary

Systems and methods are provided for providing a DMS precursor ion survey scan. An ion source configured to receive a sample is instructed to ionize the sample using a processor. A DMS device configured to receive ions from the ion source is instructed to separate precursor ions received from the ion source and transmit precursor ions using two or more CoVs using the processor. A mass analyzer configured to receive transmitted precursor ions from the DMS device is instructed to measure the m/z intensities of the transmitted precursor ions across an m/z range at each CoV of the two or more CoVs using the processor. The measured m/z intensities of the transmitted precursor ions received from the mass analyzer are stored as a function of m/z value and CoV using the processor. This produces a stored two-dimensional mapping of m/z intensities of the precursor ions of the sample.