Mass Spectrometer Real-Time Peptide Search Within Elution Time

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Solution Overview

Problem

In mass spectrometry, real-time database search (RTS) techniques face challenges in efficiently identifying peptides within the limited availability time of peptides in the mass spectrometer, leading to reduced throughput and wasted samples due to prolonged search times.

Innovation Solution

Implementing a method that monitors the elapsed search time against a predefined maximum value, allowing for quick identification of peptides and terminating the search if it exceeds this value, enabling the mass spectrometer to proceed with other operations and adjust fragmentation techniques based on candidate peptide identification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If real-time database search is performed to identify peptides quickly, then peptide identification speed is improved, but search accuracy may deteriorate due to time constraints

Engineering Contradiction:
Improvepeptide identification speedVSAvoidsearch accuracy
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The patent performs preliminary database searching during the ion introduction period before MSn analysis, preparing identification results in advance. This preliminary action allows the system to have identification results ready before the peptide is lost, resolving the contradiction by performing the search early when time is available but the peptide is still present.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements continuous database searching throughout the ion introduction period, maximizing the utilization of the brief time window when peptides are available in the mass spectrometer. This continuous action ensures that the search process runs as long as possible without exceeding the peptide availability time, balancing speed and accuracy.

Inventive Principle:
Principle #20Continuity of useful action

2Measurement precision

If database search time is extended to improve identification accuracy, then search accuracy is improved, but peptide availability time is exceeded causing sample waste

Engineering Contradiction:
Improvesearch accuracyVSAvoidsample waste
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The search is performed preliminarily during the ion introduction period, completing identification before the peptide elutes from the mass spectrometer. This prevents sample waste by ensuring the search is finished while the peptide is still available, eliminating the need to extend search beyond peptide availability.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system automatically monitors the ion introduction period and terminates the search when this period ends, using the available time efficiently without manual intervention. This self-service mechanism ensures optimal utilization of peptide availability time, preventing sample waste while maximizing identification accuracy within constraints.

Inventive Principle:
Principle #25Self-service

3Productivity

If database search is performed during ion introduction period, then throughput is improved, but device complexity increases due to real-time processing requirements

Engineering Contradiction:
Improvemass spectrometer throughputVSAvoidreal-time processing complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The database search is performed preliminarily during the ion introduction period rather than after acquisition. This timing strategy improves throughput by preparing identification results in parallel with sample introduction, eliminating sequential delays and reducing the need for complex post-processing systems.

Inventive Principle:
Principle #10Preliminary action

4Productivity

If maximum search time is set short to maintain high throughput, then throughput is improved, but identification completeness deteriorates

Engineering Contradiction:
Improvemass spectrometer throughputVSAvoididentification completeness
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The search is performed preliminarily during the ion introduction period, which provides sufficient time for complete identification without compromising throughput. This preliminary timing ensures that the search completes before peptide loss while maintaining high instrument utilization, resolving the contradiction between throughput and completeness.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3745444B1Operating a mass spectrometer utilizing mass spectral database search
Publication Date: 2024.11.13 THERMO FINNIGAN LLC
  • EP3745444B1 patent drawingFigure 1
  • EP3745444B1 patent drawingFigure 2
  • EP3745444B1 patent drawingFigure 3

AI summary

Real-time search (RTS) for mass spectrometry is described. In one aspect, a mass spectrometer can identify a candidate peptide for a product ion spectrum by searching a mass spectral database. While executing the search of the mass spectral database, the elapsed search time can be monitored. If the elapsed search time of the identification of the candidate peptide is completed before reaching a maximum value, then the mass spectrometer can perform further actions.