Mass Spectrometer Calibration Verification Using Internal Standards

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Solution Overview

Problem

Mass spectrometers in high-throughput clinical laboratory settings face challenges with instrumental drift, requiring frequent recalibrations that can delay urgent analyses, and existing calibration methods are not practical for quick adjustments.

Innovation Solution

A method for automatic calibration verification and adjustment using internal standards within routine samples, which periodically checks mass peaks of known chemical entities to determine if recalibration is necessary, allowing for minor adjustments without full re-calibration procedures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If frequent full recalibrations are performed to maintain mass spectrometer accuracy, then measurement precision is improved, but productivity deteriorates due to analysis delays

Engineering Contradiction:
Improvemass spectrometer calibration accuracyVSAvoidsample analysis throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent segments the calibration process into two distinct parts: (1) a comprehensive full calibration procedure performed periodically, and (2) a quick verification check using internal standards performed between analyses. This segmentation allows the system to maintain accuracy through frequent verification without requiring frequent time-consuming full recalibrations, thus resolving the contradiction between measurement precision and productivity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces internal standards as an intermediary substance that enables quick calibration verification. These internal standards with known mass-to-charge ratios serve as reference points to detect instrumental drift without requiring full recalibration, allowing frequent accuracy checks that maintain measurement precision while preserving sample analysis throughput

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If full recalibration procedures are performed frequently to correct instrumental drift, then reliability is improved, but loss of time increases due to recalibration delays

Engineering Contradiction:
Improvecalibration accuracy maintenanceVSAvoidrecalibration time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent implements preliminary action by adding internal standards to samples before analysis. These internal standards are prepared in advance with known characteristics, enabling immediate verification of calibration status without requiring time-consuming full recalibration procedures, thus maintaining reliability while minimizing time loss

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system uses internal standards within the sample matrix itself to self-verify calibration status. The internal standards automatically provide reference points for detecting instrumental drift, allowing the system to self-monitor and self-correct calibration issues without external intervention or time-consuming full recalibration, thereby maintaining reliability while reducing time loss

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP2786399B1Method for automated checking and adjustment of mass spectrometer calibration
Publication Date: 2019.10.09 THERMO FINNIGAN LLC
  • EP2786399B1 patent drawingFigure 1A
  • EP2786399B1 patent drawingFigure 1B
  • EP2786399B1 patent drawingFigure 2A

AI summary

A method for automatically checking and adjusting a calibration of a mass spectrometer having a first quadrupole (Ql), a fragmentation cell and a mass analyzer comprises: introducing a sample having at least one known chemical entity; decreasing a kinetic energy so as to prevent fragmentation of ions in the fragmentation cell; optionally applying a drag field to the fragmentation cell; ionizing the at least one known chemical entity sample to generate a set of ions; performing a mass scan of the set of ions using Ql; transmitting the scanned ions through Ql to and through the fragmentation cell; detecting the scanned and transmitted ions by a detector of the mass analyzer; and comparing the results with expected results. Embodiments may include automatic recalibration or notification of possible errors, need for further data processing or an analysis of system performance.