Oscillating Probe Liquid Bridge for Soft Ionization

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Solution Overview

Problem

Existing methods face challenges in ionizing macromolecules like lipids, sugars, and proteins without damaging their structure, and in achieving high spatial resolution and simplifying the apparatus for ionization, particularly in mass spectrometry of biological samples.

Innovation Solution

An ionization method using a probe that oscillates to form a liquid bridge and generate a Taylor cone for electrospray, allowing for precise control over the ionization process and improved spatial resolution under atmospheric pressure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a pointed probe is used to ionize a micro region on the sample surface, then spatial resolution is improved, but it becomes difficult to achieve soft ionization of macromolecules without structural damage

Engineering Contradiction:
Improvespatial resolutionVSAvoidstructural damage to macromolecules
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a liquid bridge as an intermediary medium between the probe and the sample surface. The liquid bridge serves as a mediator that dissolves macromolecules from the sample surface and transports them to the ionization region, preventing direct contact damage while enabling soft ionization through electrospray or laser desorption in the liquid phase

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs a liquid bridge formed by capillary action and electrohydrodynamic forces to transport dissolved macromolecules from the sample surface to the ionization region. The liquid flow system enables gentle dissolution and transport without mechanical damage, followed by soft ionization in the electrospray plume

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Measurement precision

If two capillaries are used to form a liquid bridge for micro region ionization, then spatial resolution and processing speed are improved, but apparatus complexity increases

Engineering Contradiction:
Improvespatial resolutionVSAvoidapparatus complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines the functions of solvent supply, sample dissolution, and ionization into a single integrated probe structure. The probe simultaneously serves as the solvent delivery system, the dissolution chamber, and the ionization source, eliminating the need for separate capillaries and reducing overall apparatus complexity

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The probe is designed as a multi-functional device that performs multiple operations: supplying solvent through capillary action, dissolving macromolecules at the sample surface, transporting the dissolved material, and generating ions through electrospray or laser desorption. This universal design simplifies the apparatus while maintaining high spatial resolution

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

3Productivity

If voltage and laser light are applied to a probe for ionization, then ionization efficiency is improved, but the risk of damaging biological components increases

Engineering Contradiction:
Improveionization efficiencyVSAvoiddamage to biological components
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent employs periodic oscillation of the probe at high frequency to control the formation and disruption of the liquid bridge. This periodic action allows brief contact for dissolution followed by separation for ionization, preventing overheating and cumulative damage to biological components while maintaining efficient ionization through repeated cycles

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent utilizes laser light with specific wavelength parameters that match the absorption characteristics of the liquid or probe material rather than directly targeting the sample. By changing the laser parameters (wavelength, pulse duration, intensity) and using the liquid bridge as an intermediary, efficient energy transfer is achieved without direct damage to biological macromolecules

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

This method enables efficient soft-ionization of macromolecules with enhanced spatial resolution and simplifies the apparatus, facilitating the analysis of biological samples by controlling the timing and frequency of electrospray generation.

Implementation Method 1

a first capillary configured to supply the solvent for dissolving the components in the solid sample, to the sample surface

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 2

the solvent is supplied thereto by the first capillary, whereby a liquid bridge is formed between the leading ends of the two capillaries and the sample surface

Methodology Applied
Scientific EffectLiquid bridge formation:

Implementation Method 3

A high voltage is applied to the solvent, and ionization is performed at the leading end of the second capillary

Methodology Applied
Scientific EffectElectrospray ionization: Electrohydrodynamics

Implementation Method 4

generate a Taylor cone for electrospray

Methodology Applied
Scientific EffectTaylor cone formation:

Implementation Method 5

voltage and laser light are applied to the pointed leading end of the probe, whereby only the components in the micro region that are attached to the pointed leading end of the probe can be ionized

Methodology Applied
Scientific EffectLaser desorption: Laser Ablation

Implementation Method 6

a probe that oscillates to form a liquid bridge and generate a Taylor cone for electrospray

Methodology Applied
Scientific EffectMechanical oscillation: Vibration

Data Source

PatentEP2822022B1Ionization method, mass spectrometry method, extraction method, and purification method
Publication Date: 2020.07.08 CANON KK
  • EP2822022B1 patent drawingFigure 1~2
  • EP2822022B1 patent drawingFigure 3~4D
  • EP2822022B1 patent drawingFigure 5A~6

AI summary

To achieve soft ionization more easily when a slight amount of substance is ionized under an atmosphere pressure. An ionization method for a substance contained in a liquid, including: supplying the liquid to a substrate from a probe and forming a liquid bridge made of the liquid containing the substance dissolved therein, between the probe and the substrate; oscillating the probe; and generating an electric field between an electrically conductive portion of the probe in contact with the liquid and an ion extraction electrode.