Mass Spectrometer Calibration Using Intrinsic Ion Drift Tracking
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Solution Overview
Problem
High resolution mass analyzers and mass spectrometers suffer from accuracy loss due to environmental factors like temperature fluctuations and power supply stability, leading to calibration drifts that require frequent interruptions for external calibration, which is costly and complex, and intrinsic methods risk interference with analyte species.
Innovation Solution
A method using direct calibration measurements and tracking intrinsic ion species across multiple acquisition periods to calculate calibration shifts at any time point, employing Bayesian methods to infer calibration shifts without additional interruptions, utilizing persistent or transient intrinsic ions of unknown mass-to-charge ratios.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If external lock mass calibration is performed frequently to maintain accuracy, then measurement precision is improved, but productivity deteriorates due to repeated analysis interruptions
Solution Approach 1:
The system uses intrinsic ion species naturally present in the sample to perform self-calibration during normal analysis operations, eliminating the need for external calibration interventions. The mass spectrometer calibrates itself continuously using endogenous ions, maintaining measurement precision without interrupting productivity.
Solution Approach 2:
Calibration occurs continuously during sample analysis rather than in discrete interruption cycles. By tracking intrinsic ion species throughout the entire analysis period, the system maintains continuous calibration without stopping or pausing the analytical workflow, thereby preserving both precision and productivity.
2Measurement precision
If a separate dedicated ion source is used for lock mass calibration, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The single ion source serves dual functions: it ionizes both the analyte sample and the intrinsic calibration ions simultaneously. This eliminates the need for separate dedicated ion sources for calibration, reducing device complexity while maintaining calibration accuracy through the use of intrinsic species present in the sample.
Solution Approach 2:
The calibration function is merged with the analytical function by using the same ion source and the same physical space. Intrinsic ion species from the sample are co-ionized with analyte molecules, and both are analyzed together in the mass analyzer, combining calibration and measurement into a unified process.
3Measurement precision
If external calibrants are introduced through a separate mechanism, then measurement precision is improved, but ease of operation deteriorates
Solution Approach 1:
The system automatically identifies and uses intrinsic ion species present in the sample for calibration without requiring manual introduction of external calibrants. The operator simply introduces the sample, and the system self-calibrates using endogenous ions, greatly simplifying operation while maintaining calibration reliability.
Solution Approach 2:
The calibration function is extracted from the external calibration process and embedded within the normal sample analysis. Instead of requiring separate calibration operations with external substances, the system extracts calibration information directly from the sample matrix itself, eliminating complex calibration procedures.
Data Source
AI summary
Disclosed herein is a method of processing mass spectral data comprising making direct calibration measurements to determine a calibration shift of the mass spectrometry instrument at a calibration time and determining a set of intrinsic ion species that persist across multiple acquisition periods. The direct calibration measurements are then used together with an expected variation in calibration shift as well as the set of intrinsic ion species to calculate the calibration shift of the mass spectrometry instrument at one or more time point(s) of interest other than the calibration time.