Microparticle Paper-Spray Analyte Detection for Matrix Cleanup

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Solution Overview

Problem

Biological samples such as serum, plasma, and urine often exhibit low analyte concentrations and contain matrix components that interfere with analysis, requiring effective clean-up procedures to prepare samples for mass spectrometry, while paper-based ionization techniques lack sufficient sample clean-up ability and volume applicability.

Innovation Solution

A method involving microparticles to adsorb analytes, followed by using a fiber sheet material to suck in the analyte-microparticle-complex, apply an extracting solvent, and generate ions for detection with an analytical device, including steps like centrifugation and magnetic separation for sample preparation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If paper-based ionization techniques are used, then the analysis of biological samples is simplified and transport/storage is easier, but the sample clean-up ability is insufficient and matrix components interfere with detection

Engineering Contradiction:
Improvesample preparation simplicityVSAvoidmatrix interference
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The system divides the sample preparation process into distinct functional segments: the fiber sheet material performs clean-up and concentration, while the paper substrate performs ionization. This segmentation allows each component to optimize its specific function without compromise.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The fiber sheet material acts as an intermediary between the complex biological sample and the paper spray ionization source. It pre-processes the sample by adsorbing analytes and removing matrix components before the sample reaches the ionization interface.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Device complexity

If traditional paper spray is used, then the device complexity is low and cost is reduced, but the detection sensitivity is insufficient due to low analyte concentrations in biological samples

Engineering Contradiction:
Improvesystem simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The fiber sheet material performs preliminary concentration of analytes from large sample volumes before ionization. This pre-concentration step increases analyte signal intensity without requiring complex post-processing equipment.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The fiber sheet material utilizes its porous structure to adsorb and concentrate analytes from the sample matrix, enhancing detection sensitivity through physical concentration before the ionization step.

Inventive Principle:
Principle #31Porous materials

3Object-affected harmful factors

If microparticles are added for clean-up, then the sample purification is improved, but the device complexity and processing time increase

Engineering Contradiction:
Improvematrix removalVSAvoidsystem complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The system merges multiple functions into the fiber sheet material: adsorption of analytes, removal of matrix components, concentration of analytes, and delivery to the ionization source. This consolidation avoids the need for separate processing steps and equipment.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The fiber sheet material serves multiple functions simultaneously: it acts as an adsorbent for analyte capture, a filter for matrix removal, a concentrator for signal enhancement, and a transport medium to the ionization interface.

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

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 method effectively cleans up and concentrates analytes from complex samples, enhancing the signal intensity and improving the detection sensitivity of analytes in biological samples, while effectively addressing the challenges of low concentration and interference from matrix components.

Implementation Method 1

incubating the sample with microparticles having at least one surface whereby the analyte is adsorbed on the surface of the microparticles

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

contacting the tip of the fiber sheet material to the sample comprising the analyte-microparticle-complex whereby at least the analyte-microparticle-complex is sucked into the tip of the fiber sheet material

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 3

adding an extracting solvent to the fiber sheet material and applying an electrical voltage to the fiber sheet material whereby ions of the analyte are generated

Methodology Applied
Scientific EffectElectrospray ionization: Electrostatics

Data Source

PatentEP4359754B1Method for detecting at least one analyte in a sample
Publication Date: 2026.03.11 F HOFFMANN LA ROCHE & CO AG
  • EP4359754B1 patent drawingFigure 1A~1D
  • EP4359754B1 patent drawingFigure 1E~1H
  • EP4359754B1 patent drawingFigure 2A~2C

AI summary

A method for detecting at least one analyte (110) in a sample (112) is disclosed. The method comprises the following steps: a) providing at least one sample (112) having at least one analyte (110); b) incubating the sample (112) with microparticles (118) having at least one surface (120) whereby the analyte (110) is adsorbed on the surface (120) of the microparticles (118) and an analyte-microparticle-complex (122) is formed; c) providing at least one fiber sheet material (128) having at least one tip (130) and contacting the tip (130) of the fiber sheet material (128) to the sample (112) comprising the analyte-microparticle-complex (122), whereby at least the analyte-microparticle-complex (122) is sucked into the tip (130) of the fiber sheet material (128); d) contacting the tip (130) of the fiber sheet material (128) to a port of an analytical device; e) adding an extracting solvent (138) to the fiber sheet material (128) and ap¬ plying an electrical voltage to the fiber sheet material (128) whereby ions of the analyte (110) are generated and are expelled from the tip (130) of the fiber sheet material (128); and f) detecting the at least one analyte (110) with the analytical device (134).