Parallel Isolation Multiplexing for High-Selectivity DIA Mass Spectrometry

Solution Overview

Problem

Existing data-independent acquisition (DIA) techniques in mass spectrometry face challenges in balancing isolation width, precursor m/z range, and acquisition cycle time, leading to issues such as the 'missing value problem, compromised data quality, and difficulty in interpreting complex spectra due to co-isolation and co-fragmentation of neighboring analytes.

Innovation Solution

A system and method for DIA with parallel isolation multiplexing, where the precursor m/z range is divided into non-contiguous isolation sub-windows, allowing each window unit to be analyzed multiple times, improving sensitivity and selectivity by using a wide parallel isolation width and incorporating m/z gaps between sub-windows.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If a wide isolation width is used in DIA, then a wider precursor m/z range can be analyzed, but data quality is compromised due to co-isolation and co-fragmentation of neighboring analytes

Engineering Contradiction:

Improveprecursor ion species rangeVSAvoiddata quality

Core Design Contradiction:

Quantity of substanceVSMeasurement precision

Solution Approach 1:

The precursor m/z range is divided into multiple non-contiguous isolation sub-windows rather than using a single continuous wide window. This segmentation allows the system to analyze a wide overall m/z range while maintaining narrow effective isolation widths for each sub-window, preventing co-isolation and co-fragmentation of neighboring analytes.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces a temporal dimension by analyzing each isolation window unit multiple times throughout the acquisition cycle. This multi-pass approach allows comprehensive coverage of the precursor m/z range while maintaining high selectivity in each individual analysis, effectively adding a time dimension to resolve the spatial contradiction between wide range and narrow window.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Measurement precision

If a narrow isolation width is used, then data quality with greater sensitivity is achieved, but fewer precursor ion species can be analyzed

Engineering Contradiction:

Improvedata qualityVSAvoidprecursor ion species range

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The precursor m/z range is divided into multiple non-contiguous isolation sub-windows rather than using a single continuous wide window. This segmentation allows the system to analyze a wide overall m/z range while maintaining narrow effective isolation widths for each sub-window, preventing co-isolation and co-fragmentation of neighboring analytes.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The acquisition cycle is repeated multiple times, with each isolation window unit being analyzed at least twice during the cycle. This continuous multi-pass analysis ensures that all precursor ion species are captured with high sensitivity while maintaining comprehensive coverage of the precursor m/z range through the combination of multiple narrow sub-windows.

Inventive Principle:

Principle #20Continuity of useful action

3Productivity

If the acquisition cycle time is reduced to increase throughput, then productivity improves, but the precursor m/z range cannot be completely sampled

Engineering Contradiction:

Improveacquisition throughputVSAvoidprecursor m/z range coverage

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The precursor m/z range is divided into multiple non-contiguous isolation sub-windows that can be analyzed in parallel or in a compressed sequential manner within a single acquisition cycle. This segmentation enables complete sampling of the precursor m/z range in shorter cycle times while maintaining comprehensive coverage.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces a temporal dimension by analyzing each isolation window unit multiple times throughout the acquisition cycle. This multi-pass approach allows comprehensive coverage of the precursor m/z range while maintaining high selectivity in each individual analysis, effectively adding a time dimension to resolve the spatial contradiction between wide range and narrow window.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Data Source

PatentUS12567573B2Data independent acquisition with parallel isolation multiplexing

Publication Date: 2026.03.03 THERMO FINNIGAN LLC

AI summary

A system may control a mass spectrometer to acquire, during a plurality of acquisitions constituting an acquisition cycle, a set of mass spectra of product ions derived from precursor ions isolated based on a parallel isolation window successively positioned throughout a precursor mass-to-charge ratio (m/z) range. The precursor m/z range is divided into a plurality of isolation window units. The parallel isolation window includes, for each acquisition of the acquisition cycle, a set of isolation sub-windows corresponding to a distinct set of isolation window units of the precursor m/z range. At least two adjacent isolation sub-windows of the parallel isolation window are non-contiguous. Each isolation window unit of the precursor m/z range is analyzed at least twice during the acquisition cycle. A mass spectrum for the precursor m/z range may be generated based on the set of mass spectra acquired during the acquisition cycle.