Paper Chromatography Substrate for Matrix-Reduced Paper Spray MS

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Solution Overview

Problem

Paper spray mass spectrometry (PS-MS) has not been incorporated into routine clinical practice due to significant signal suppression caused by matrix effects during ionization, particularly when analyzing complex biological matrices, which hinders its introduction into bedside monitoring.

Innovation Solution

A method combining paper chromatography (PC) and paper-spray mass-spectrometry (PS-MS) on a monolithic substrate, such as paper, to separate analytes from the matrix, using a mobile phase, and utilizing the substrate as an ion source for analysis, thereby reducing matrix interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If direct analysis of complex biological matrices is performed using PS-MS, then rapid and cost-effective analysis is achieved, but signal suppression caused by matrix effects occurs during ionization

Engineering Contradiction:
Improveanalysis speedVSAvoidquantitation precision
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The substrate is divided into multiple zones: a separation zone where chromatography occurs and an ionization zone where mass spectrometry occurs. This spatial segmentation allows analytes to be separated from matrix components before ionization, reducing matrix effects while maintaining rapid analysis capability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Matrix components are extracted or removed from the sample during the chromatography separation process on the substrate. By separating the analyte from the complex biological matrix before ionization, the harmful matrix effects are eliminated while preserving the rapid analysis advantage.

Inventive Principle:
Principle #2Taking out (Extraction)

2Measurement precision

If separation procedures are added to reduce matrix effects, then quantitation precision is improved, but analysis time and complexity increase

Engineering Contradiction:
Improvequantitation precisionVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

Chromatography separation and mass spectrometry ionization are merged into a single integrated substrate. The mobile phase flows through the substrate carrying separated analytes directly to the ionization zone, eliminating the need for separate transfer steps and maintaining rapid analysis while achieving precise quantitation.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The substrate serves multiple functions simultaneously: it acts as the chromatography medium for separation, the mobile phase delivery system, and the ionization source. This multi-functionality reduces procedural steps and analysis time while ensuring precise separation and detection.

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

3Device complexity

If the same substrate is used for both chromatography and ionization, then device complexity is reduced, but the substrate must perform multiple functions simultaneously

Engineering Contradiction:
Improvesystem complexityVSAvoidfunctional versatility
Core Design Contradiction:
Device complexityVSAdaptability or versatility

Solution Approach 1:

The substrate is designed to perform multiple functions: chromatography separation, mobile phase transport, and electrospray ionization. By making the substrate itself multi-functional, the system complexity is reduced without sacrificing analytical performance or adaptability to different analytes.

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

Solution Approach 2:

The substrate is configured with distinct spatial zones (separation zone and ionization zone) along the flow path. This dimensional arrangement allows different functions to occur simultaneously in different regions of the same substrate, resolving the conflict between simplicity and multi-functionality.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 achieves rapid, cost-effective, and precise quantitation of analytes in biological samples, enabling portable MS analysis suitable for clinical scenarios like overdose detection and treatment monitoring, with improved limits of detection and quantification.

Implementation Method 1

separating the analytes, for example mutually and/or relative to the matrix, on the substrate using a mobile phase

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

the substrate provides, at least in part, an ion source for ionising the separated analytes

Methodology Applied
Scientific EffectIonization: Ionisation

Data Source

PatentUS20250362316A1Apparatus and method
Publication Date: 2025.11.27 UNIV OF LIVERPOOL
  • US20250362316A1 patent drawing
  • US20250362316A1 patent drawing
  • US20250362316A1 patent drawing

AI summary

A method comprising:providing a sample comprising analytes, for example in a matrix, on a substrate, for example a monolithic substrate, comprising a stationary phase;separating the analytes, for example mutually and/or relative to the matrix, on the substrate using a mobile phase; andanalysing the separated analytes using mass spectrometry, wherein the substrate provides, at least in part, an ion source for ionising the separated analytes.