SPE Extract Evaporation for Sensitive LC-MS Sample Preparation

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Solution Overview

Problem

Existing sample preparation methods for mass spectrometry, particularly involving solid phase extraction (SPE), suffer from significant analyte loss due to dead volumes and the need to minimize organic solvent content, leading to reduced sensitivity and inefficiency in analyte detection.

Innovation Solution

A method involving partial evaporation of solvent from the SPE extract to concentrate the analyte, followed by dilution with a low-organic solvent solution, and subsequent detection using mass spectrometry, specifically LC-MS.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the SPE extract is diluted with water to reduce organic solvent content, then chromatographic performance is improved, but analyte detection sensitivity deteriorates due to further analyte loss

Engineering Contradiction:
Improvechromatographic performanceVSAvoidanalyte detection sensitivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies evaporation (phase transition from liquid to gas) to remove excess organic solvent from the SPE extract. By partially evaporating the solvent under controlled conditions, the organic solvent content is reduced to acceptable levels for LC-MS analysis while concentrating the analyte, thereby avoiding the sensitivity loss that would occur with aqueous dilution.

Inventive Principle:
Principle #36Phase transitions

2Reliability

If the SPE extract is evaporated to remove organic solvent, then chromatographic performance is improved, but sample preparation time increases

Engineering Contradiction:
Improvechromatographic performanceVSAvoidsample preparation time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent employs partial evaporation rather than complete evaporation or full concentration. By removing only the excess organic solvent portion (achieving 50-90% solvent reduction), the method achieves sufficient chromatographic performance while significantly reducing the time required compared to complete evaporation and reconstitution protocols.

Inventive Principle:
Principle #16Partial or excessive action

3Loss of substance

If dead volume is minimized in transfer and injection processes, then analyte loss is reduced, but device complexity increases

Engineering Contradiction:
Improveanalyte lossVSAvoidsystem complexity
Core Design Contradiction:
Loss of substanceVSDevice complexity

Solution Approach 1:

The patent integrates the concentration step into the sample preparation workflow by performing partial evaporation directly in the SPE extract vial or a single concentrated vessel. This eliminates the need for multiple transfer steps between separate concentration and analysis vessels, thereby minimizing dead volume losses while avoiding the complexity of multi-vessel automated systems.

Inventive Principle:
Principle #5Merging (Combining)

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

This approach enhances analyte recovery and detection sensitivity, reduces sample preparation time, and maintains optimal chromatographic performance by minimizing organic solvent interference, suitable for automated systems.

Implementation Method 1

concentrating the analyte by partially evaporating solvent from the SPE-extract obtained in a)

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentUS12504405B2Evaporation-based sample preparation workflow for mass spectrometry
Publication Date: 2025.12.23 ROCHE DIAGNOSTICS OPERATIONS INC
  • US12504405B2 patent drawing
  • US12504405B2 patent drawing
  • US12504405B2 patent drawing

AI summary

The present invention relates to a method for detecting and/or quantifying an analyte in a sample using mass spectrometry. The method of the invention comprises: extracting the analyte from the sample using solid phase extraction (SPE) so as to obtain an SPE extract comprising the analyte, concentrating the analyte, said concentrating comprising evaporating solvent from the SPE-extract; and detecting and/or quantifying the analyte in the sample using mass spectrometry.