Mass Spectrometer Linearity Assessment Using Isomeric Standards

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Solution Overview

Problem

Current methods for determining linearity and extending the quantitative range in mass spectrometry are time-consuming, prone to errors, and costly, particularly due to issues with analyte carryover, co-elution, and the need for multiple calibration standards, which complicates the assessment of instrument sensitivity and dynamic range.

Innovation Solution

A method involving positional isomers composited in a single standard at varying concentrations, allowing for linearity assessment in two to three analysis runs, with the option to use internal standards for correction, and employing isomer interleaving to minimize carryover and co-elution effects, thereby reducing the number of standards required and improving analysis efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multiple calibration standards are used to determine linearity across several orders of magnitude, then measurement precision is improved, but loss of time increases due to multiple analytical runs and component changes

Engineering Contradiction:
Improvelinearity assessment accuracyVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent combines multiple calibration standards into a single multi-component standard containing several analytes at different concentrations. This allows linearity assessment across multiple orders of magnitude to be performed in fewer analytical runs, eliminating the need to sequentially inject separate standards and reducing component change frequency while maintaining measurement precision.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent segments the concentration range into multiple levels within a single standard, with each analyte representing a different concentration decade. This segmentation allows comprehensive linearity evaluation across the full dynamic range to be achieved in one injection rather than requiring multiple separate injections of single-standard solutions.

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If high concentration standards are used to extend dynamic range, then measurement precision is improved at high levels, but object-generated harmful factors increase due to analyte carryover and contamination

Engineering Contradiction:
Improvehigh concentration quantitation accuracyVSAvoidanalyte carryover
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts high concentration analytes into separate waste collection vials during the analytical run. This isolation prevents carryover of high concentration standards to subsequent low concentration injections, eliminating contamination issues while maintaining the ability to accurately quantify high concentration samples in the extended dynamic range.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces a waste collection vial as an intermediary between the analytical column and the detector for high concentration standards. This intermediary captures and isolates the harmful high concentration analytes, preventing them from contaminating the system and affecting subsequent analyses, while still allowing their quantitation.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If frequent component changes and baking procedures are performed to eliminate carryover, then reliability is improved, but loss of time increases and device complexity increases

Engineering Contradiction:
Improveinstrument cleanlinessVSAvoidmaintenance time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent implements an automated waste collection system that self-manages the isolation and containment of high concentration analytes during normal operation. This eliminates the need for manual intervention through frequent component changes and baking procedures, maintaining instrument reliability while reducing maintenance time and operational complexity.

Inventive Principle:
Principle #25Self-service

4Manufacturing precision

If proper dilution techniques are used across several orders of concentration, then manufacturing precision is improved, but loss of time increases due to the tedious dilution process

Engineering Contradiction:
Improvedilution accuracyVSAvoidstandard preparation time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent combines multiple dilution steps into a single standard preparation process, where several analytes at different concentration levels are composited together in one procedure. This eliminates the need for sequential dilution of individual standards and reduces preparation time while maintaining the precision required for accurate quantitation across the full concentration range.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentUS10598641B2Methods for determining instrument linearity and quantification
Publication Date: 2020.03.24 THERMO FINNIGAN LLC
  • US10598641B2 patent drawing
  • US10598641B2 patent drawing
  • US10598641B2 patent drawing

AI summary

A method of assessing the linearity and dynamic range of a mass spectrometer is described comprising analyzing two or more test standards containing positional isomers, for example, using a series of N isomeric analytes with or without an internal standard where N is an integer from 2 to 6 inclusive. The concentrations of the N isomeric analytes may or may not be interleaved between two or more standards. The method allows for repeated instrument characterization without having many of the problems associated with using only a single standard such as octafluoronaphthalene (OFN), for example, persistence, and it may lessen sample carryover issues between adjacent samples. Methods are described using positional isomers of dibromodifluorobenzene in various configurations that show an improved means for qualitative and quantitative analysis of one or more analytes by GC-MS.