Chemical Coding for Sample Identity in LC-MS

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Solution Overview

Problem

Ensuring traceability of sample identity during complex, highly parallelized, and random access sample preparation processes in liquid chromatography coupled to tandem mass spectrometry is challenging, particularly in multiplexed HPLC-MS systems where sample identity relies on correct timing and positioning of diverting valves.

Innovation Solution

A method for tracking sample identity involves adding a composition of chemical substances with unique coding properties to each sample during the sample preparation process. These substances are designed to follow the sample through the workflow, ensuring unambiguous identification by the mass spectrometer, even in high-throughput and multiplexed systems.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple samples are processed in parallel using multiplexed HPLC-MS systems, then productivity is improved, but reliability of sample identity tracking deteriorates due to complex flow path management

Engineering Contradiction:
ImprovethroughputVSAvoidsample identity tracking
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces chemical coding substances as intermediaries that are added to samples before processing. These substances act as mediators between the sample and the detection system, providing a reliable identifier that travels with the sample through the complex parallel flow paths. The coding substances enable unambiguous sample identification even when multiple samples are processed simultaneously, resolving the conflict between high throughput and reliable tracking.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical system of tracking sample identity through timing and valve positioning with a chemical coding system. Instead of relying on mechanical control of flow paths and timing, the system uses chemical markers that inherently identify each sample. This substitution eliminates the reliability issues associated with mechanical flow path management in multiplexed systems while maintaining high productivity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If correct timing and positioning of diverting valves is used to maintain sample identity, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
Improvesample identity identificationVSAvoidflow path control system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the complex mechanical valve control system with a simpler chemical coding approach. Instead of using diverting valves and precise timing to track samples, the system adds chemical codes that passively identify each sample throughout the process. This eliminates the need for complex mechanical flow path control while maintaining precise sample identification.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent creates a chemical copy or representation of sample identity through coding substances. Rather than physically tracking the sample through mechanical means, the system creates a chemical identifier that replicates the sample's identity information and follows it through the analysis process. This copying approach simplifies the device while maintaining measurement precision.

Inventive Principle:
Principle #26Copying

3Ease of operation

If manual sample preparation procedures are used, then ease of operation is maintained, but productivity deteriorates due to time-consuming processes

Engineering Contradiction:
Improvesample preparationVSAvoidthroughput
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The patent implements a universal chemical coding system that can be applied to multiple samples simultaneously through automated liquid handling. The coding substances are designed to work with high-throughput sample preparation methods, enabling automated processing of many samples while maintaining ease of operation through standardized procedures. This universal approach allows parallel processing without sacrificing operational simplicity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Productivity

If kits are used to automate sample preparation, then productivity is improved, but adaptability deteriorates due to limited analyte coverage

Engineering Contradiction:
Improveautomation throughputVSAvoidanalyte coverage
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent uses a modular chemical coding system where the identity information is encoded through variations in chemical parameters such as mass-to-charge ratio. This parameter-based encoding allows the same automated platform and chemistry to be used for different analytes by simply changing the coding substances. The system can be adapted to different analytes without requiring different kits, maintaining both high productivity and versatility.

Inventive Principle:
Principle #35Parameter changes

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

The method enables reliable and convenient tracking of sample identity throughout the analysis process, facilitating high-throughput and random access sample preparation while reducing the need for manual intervention and minimizing user-dependent variability.

Implementation Method 1

liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 2

liquid chromatography coupled to tandem mass spectrometry

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP3559656B1Method for tracking a sample identity during a process in an analysis system
Publication Date: 2025.04.02 ROCHE DIAGNOSTICS GMBH
  • EP3559656B1 patent drawingFigure 1~2
  • EP3559656B1 patent drawingFigure 3
  • EP3559656B1 patent drawingFigure 4

AI summary

A method for tracking a sample identity during a process in an analysis system (112) is disclosed. The analysis system (112) comprises a liquid chromatograph (102) and a mass spectrometer (104). The method comprises providing a sample (108), adding a composition (130) of different chemical substances (132) to the sample (108) with a concentration being above a detection level of the mass spectrometer (104), processing the sample (108) together with the composition (130) by means of the analysis system (112), detecting and measuring a component and/or components of the sample (108) by means of the mass spectrometer (104), detecting and measuring the composition (130) or parts of the composition (130) of different chemical substances (132) by means of the mass spectrometer (104), and identifying the sample (108) based on a detection of a substance detection signal pattern of the mass spectrometer (104) including substance detection signals representing the composition (130) of chemical substances (132).