Tandem Mass Spectrometry Dynamic Range via Time-Encoded Pulsing

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Solution Overview

Problem

Current tandem mass spectrometry (MS-MS) instruments face limitations in dynamic range and compound identification when analyzing complex mixtures, such as proteome samples, due to limited time for full mass range analysis and dynamic range constraints in data-dependent and independent acquisition strategies.

Innovation Solution

The method involves ramping or stepping a wide parent mass window in the first mass spectrometer, arranging rapid ion transfer through a collisional cell, frequently pulsing an orthogonal accelerator with time-encoded pulses, and analyzing fragment ions in a multi-reflecting time-flight mass spectrometer to decode signal strings corresponding to the entire scan of parent masses, thereby enhancing dynamic range without limiting parent masses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If data dependent acquisition is used to identify parent ions, then compound identification capability is improved, but dynamic range is limited due to observation time constraints

Engineering Contradiction:

Improvecompound identification capabilityVSAvoiddynamic range

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent implements periodic action by rapidly cycling through multiple parent mass windows in a systematic sequence, allowing the system to sample different mass ranges repeatedly over time. This periodic scanning approach enables coverage of a broader dynamic range while maintaining identification capability through time-correlated fragment analysis.

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent adds a time dimension to the analysis by recording time-correlated fragment spectra for each parent mass window scan. This temporal dimension allows reconstruction of complete mass spectra from fragmented data, effectively expanding the dynamic range without sacrificing identification precision.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Productivity

If full mass range analysis is performed quickly, then analysis speed is improved, but dynamic range and sensitivity are reduced

Engineering Contradiction:

Improveanalysis speedVSAvoiddynamic range

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent segments the full mass range into multiple smaller parent mass windows that are scanned sequentially. This segmentation allows each window to be analyzed with sufficient dwell time for high sensitivity, while the collective coverage of all windows achieves comprehensive mass range analysis at high speed.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent maintains continuous useful action by systematically overlapping and cycling through multiple parent mass windows without idle time. The rapid switching between windows ensures that the analyzer is continuously acquiring useful data across the entire mass range, maximizing productivity while preserving dynamic range.

Inventive Principle:

Principle #20Continuity of useful action

3Measurement precision

If MS1 window is narrowed to observe specific parent ions, then measurement precision is improved, but the number of detectable compounds is reduced

Engineering Contradiction:

Improveparent ion observation precisionVSAvoidnumber of detectable compounds

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent implements universality by designing a multi-function scanning system that can observe multiple parent ion species across different mass ranges using the same analytical approach. Each parent mass window is configured to detect its specific target ions with high precision, while the systematic cycling through all windows provides universal coverage of the entire mass range.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 significantly increases the dynamic range of analyzed compounds, enhancing sensitivity and resolution, allowing for the identification of a larger number of parent ions and improving the separation power for proteomics analysis, with a 10-fold enhancement in dynamic range and sensitivity compared to conventional systems.

Implementation Method 1

subjected to fragmentation, usually in collisional induced dissociation (CID) cell

Methodology Applied

Scientific EffectCollisional induced dissociation (CID):

Implementation Method 2

analyzing fragment ions in a multi-reflecting time-flight mass spectrometer

Methodology Applied

Scientific EffectTime of flight: Time of Flight

Data Source

PatentUS9779923B2Method and system for tandem mass spectrometry

Publication Date: 2017.10.03 LECO CORP

AI summary

A method of data independent MS-MS analysis is disclosed. The method comprises ramping or stepping in small steps of a wide (at least 10 amu) parent mass window in a first parent selecting mass spectrometer (MS1), arranging rapid ion transfer through a collisional cell, either by axial gas flow or by an axial DC field or by a travelling RF wave, frequently pulsing an orthogonal accelerator with a string of time-encoded pulses, analyzing fragment ions in a multi-reflecting time-flight mass spectrometer, acquiring data in a data logging format, and decoding signal strings corresponding to the entire scan of parent masses, such that fragment spectra are formed based on time correlation between fragment and parent masses. Frequent pulsing is expected to recover parent and fragment time correlation with an accuracy of approximately 1 Th, in spite of using much wider mass window in the first MS.