Nanoparticle Tag Counting by LA-ICP-MS Without Particle Disintegration

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Solution Overview

Problem

Current methods for detecting nanoparticle tags in biological samples using laser ablation inductively coupled plasma mass spectrometry (LA ICP MS) face limitations, including the disintegration of nanoparticles during the ablation process, which prevents accurate counting and detection of individual particles, especially when present in low numbers or as part of a mixture.

Innovation Solution

The method employs a specific wavelength, typically in the infrared range, or an auxiliary absorbing component to prevent nanoparticle disintegration during laser ablation, allowing for the detection of inorganic nanoparticle tags without forming a plume, enabling the use of a virtually unlimited number of nanoparticle types and improving detection sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional laser ablation is used for nanoparticle detection, then the ablation process can be performed, but the nanoparticles disintegrate and form a plume preventing accurate counting

Engineering Contradiction:
Improvenanoparticle integrityVSAvoidnanoparticle counting accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent changes the laser wavelength parameter from conventional UV/visible ranges to mid-infrared range (2-10 μm), which fundamentally alters the interaction mechanism between laser and nanoparticles. This parameter change prevents nanoparticle disintegration while maintaining ablation capability for accurate detection and counting.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an auxiliary absorbing component as an intermediary substance that absorbs the laser energy and transfers it to the sample matrix without directly affecting the nanoparticles. This mediator enables the ablation process to proceed while protecting nanoparticle integrity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If the number of metal atoms per tag is increased to boost sensitivity, then detection sensitivity improves, but the tag size increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtag size
Core Design Contradiction:
Measurement precisionVSVolume of moving object

Solution Approach 1:

The patent changes the detection parameter from relying on signal amplification through multiple metal atoms to direct single-particle detection using mid-infrared laser ablation. This allows using smaller nanoparticles with fewer metal atoms while maintaining high detection sensitivity through the enhanced detection capability of the new method.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If UV laser is used for ablation, then ablation can be performed, but nanoparticle disintegration occurs preventing single-particle detection

Engineering Contradiction:
Improveablation efficiencyVSAvoidnanoparticle integrity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent changes the laser wavelength parameter from UV to mid-infrared range, which fundamentally alters the ablation mechanism. The mid-infrared laser achieves effective ablation through different physical interactions that do not cause nanoparticle disintegration, maintaining both productivity and reliability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an auxiliary absorbing component as a mediator that absorbs the laser energy and facilitates the ablation process without directly interacting with the nanoparticles in a way that causes disintegration, thereby maintaining nanoparticle integrity during efficient ablation.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 allows for the accurate counting and detection of individual inorganic nanoparticle tags, even when present in low numbers, by preventing disintegration and ensuring sharp spike signals in ICP MS, thereby enhancing the versatility and sensitivity of nanoparticle detection in biological samples.

Implementation Method 1

irradiating a spot in the sample by a laser beam emitted by a laser emitting at the at least one predetermined wavelength, thereby exciting and ablating the absorbing component on the illuminated spot

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Implementation Method 2

having a laser beam emitted by a laser emitting at least one predetermined wavelength, wherein the nanoparticle tags do not absorb at the at least one predetermined wavelength

Methodology Applied
Scientific EffectAbsorption of electromagnetic radiation: Absorption (EM radiation)

Implementation Method 3

transferring the desorbed intact nanoparticle tags into an ICP torch, subjecting them to inductively coupled plasma mass spectrometry, and detecting characteristic spike signals of the individual nanoparticle tags

Methodology Applied
Scientific EffectInductively coupled plasma mass spectrometry: Electromagnetic Induction

Data Source

PatentEP4297063A1Method of counting nanoparticle tags in solid samples
Publication Date: 2023.12.27 MASARYK UNIVERSITY
  • EP4297063A1 patent drawingFigure 1a~1b
  • EP4297063A1 patent drawingFigure 2a~2d
  • EP4297063A1 patent drawingFigure 3a~3d

AI summary

The invention provides a method of counting inorganic nanoparticle tags in a sample, using laser ablation inductively coupled plasma mass spectrometry (LA ICP MS), comprising the steps of: a) providing a sample containing inorganic nanoparticle tags, said sample having at least one absorbing component capable of absorbing the energy of a laser at least one predetermined wavelength, b) irradiating a spot in the sample by a laser emitting at the at least one predetermined wavelength, thereby exciting and ablating the absorbing component on the illuminated spot, thereby causing desorption of the inorganic nanoparticle tag(s) which are present in the irradiated spot without disintegrating the inorganic nanoparticle tag(s), c) transferring the desorbed inorganic nanoparticle tag(s) into an ICP torch, subjecting it to inductively coupled plasma mass spectrometry, and detecting spike(s) of the individual inorganic nanoparticle tag(s); d) optionally repeating steps b) and c).