Mass Spectrometry Subgroup Identification With Peak Shift Correction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing mass spectrometry methods struggle to accurately differentiate between closely related microorganisms at subspecies or strain levels due to variability in peak positions and signal suppression, limiting identification precision.
Innovation Solution
A method and device for mass spectrometry that builds knowledge bases and classification models to correct mass-on-charge shifts, allowing identification of microorganisms at the subgroup level without additional sample preparation or standard use, using statistical analysis and adjustment models to refine peak positions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If external calibration is used to calibrate the mass spectrometer, then the measurement process is simple and quick, but the measurement precision is insufficient for subspecies-level identification
Solution Approach 1:
The patent applies preliminary action by performing calibration using internal standards that are incorporated into the sample matrix before analysis. This pre-calibration approach ensures that the mass-on-charge measurements are accurately corrected for instrumental drift and variability, enabling precise subspecies-level identification without requiring time-consuming external calibration procedures for each sample.
Solution Approach 2:
The patent uses internal calibration standards as intermediaries between the sample and the detection system. These known reference compounds are co-analyzed with the sample, serving as mediators to establish accurate mass-to-charge ratio relationships. This intermediary approach allows the system to achieve high measurement precision while maintaining operational efficiency.
2Measurement precision
If internal calibration standards are used to improve measurement precision, then mass-on-charge accuracy improves, but signal suppression occurs due to excessive standard concentration
Solution Approach 1:
The patent applies parameter changes by optimizing the concentration of internal calibration standards to a level that is sufficient for accurate mass-on-charge measurement but below the threshold that causes signal suppression. This parameter optimization allows the system to achieve high measurement precision while avoiding the harmful effect of signal suppression from excessive standard concentration.
3Productivity
If classification is performed only at the species level, then the identification process is simple and fast, but the identification precision is insufficient for closely related microorganisms
Solution Approach 1:
The patent applies segmentation by dividing the identification process into two hierarchical levels: species-level classification followed by subspecies-level classification. This segmented approach allows the system to first quickly identify the species, then apply more refined analysis only when needed for closely related microorganisms, thereby maintaining both speed and precision.
Solution Approach 2:
The patent implements a dynamic identification process that adapts the level of analysis based on the sample characteristics. When spectra indicate closely related microorganisms, the system dynamically transitions from simple species-level identification to more complex subspecies-level analysis, optimizing both identification speed and precision according to the specific sample requirements.
4Device complexity
If mass spectra variability is not corrected, then the analysis process is simple, but peak position variability prevents accurate subgroup differentiation
Solution Approach 1:
The patent applies feedback by using the measured positions of internal calibration standards to correct peak positions in the sample spectra. This feedback mechanism continuously monitors and compensates for mass-on-charge drift, ensuring accurate peak position determination for subgroup differentiation while maintaining a relatively simple analysis process.
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
Enhances the accuracy of microorganism identification to the subgroup level, reducing variability and maintaining precision while being cost-effective and time-efficient, compatible with existing protocols.
Implementation Method 1
The invention relates to the field of classification of microorganisms, particularly bacteria, using spectrometry. The invention is particularly applicable to the identification of microorganisms using mass spectrometry, for example MALDI-TOF (Matrix-assisted laser desorption/ionization time of flight).
Implementation Method 2
In MALDI-TOF spectrometry, the matrix (α-cyano-4-hydroxycinnamic acid (α-HCCA), etc.) is deposited on the sample and standard mixture to co-crystallize them.
Data Source
Figure 1
Figure 2
Figure 3a
AI summary
Method for identifying by mass spectrometry an unknown microorganism subgroup from among a set of reference subgroups, comprising a step of constructing a knowledgebase and a model allowing classification by associated subgroup, which step is carried out on the basis of at least one acquired set of training spectra taken from microorganisms identified as belonging to subgroups of a group, said step comprising: constructing an adjusting model allowing shifts in mass-to-charge ratio of the acquired spectra to be corrected on the basis of reference mass-to-charge ratios common to the various subgroups; adjusting the mass-to-charge ratios of all of the lists of peaks of the training spectra; and constructing a model allowing classification by subgroup and the associated knowledgebase on the basis of the adjusted training spectra.