Ambient Ionization Tissue Imaging for Automated Spectral Mapping

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Solution Overview

Problem

Conventional rapid evaporative ionization mass spectrometry for tissue analysis requires manual sampling and histological validation, leading to uncertainty due to the evaporation of tissue samples, which limits the accuracy of spectral data and interpolation-based identification methods.

Innovation Solution

An automated computer-controlled method for ambient ionization mass spectrometry sampling allows for 3D tissue environment validation, enabling systematic and high-throughput data collection from macroscopic tissue slices without the need for prior sample preparation, using a 2D stage with a high-precision z-axis actuator and ambient ionization techniques like laser ablation electrospray ionization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If manual electrosurgical sampling is used for tissue analysis, then spectral data can be obtained for histopathological characterization, but tissue evaporation during analysis causes uncertainty and reduces identification accuracy

Engineering Contradiction:
Improvespectral data accuracyVSAvoididentification reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies preliminary action by performing automated ambient ionization mass spectrometry imaging on macroscopic tissue slices before histological processing. This creates a spectral library with spatial coordinates that can be correlated with subsequent histological findings, allowing validation of spectral interpretations without the tissue being completely evaporated or lost.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent creates a spectral copy or map of the tissue's molecular composition through ambient ionization mass spectrometry imaging. This spectral map serves as a duplicate information layer that can be overlaid with histological images, allowing researchers to validate findings without needing the original physical tissue to remain intact after evaporation-based analysis.

Inventive Principle:
Principle #26Copying

2Productivity

If automated ambient ionization mass spectrometry imaging is used, then high-throughput data collection from macroscopic tissue slices is enabled, but complex instrumentation with 2D stage and z-axis actuator is required

Engineering Contradiction:
Improvedata collection throughputVSAvoidinstrumentation complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs a laser ablation electrospray ionization (LAESI) source that can operate in multiple modes: automated imaging mode for high-throughput data collection and manual pointing mode for targeted analysis. This multi-functionality allows the same instrument to perform both automated mapping and focused investigation, reducing the need for separate specialized devices.

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

Solution Approach 2:

The automated ambient ionization mass spectrometry imaging system performs self-positioning and self-mapping of tissue regions through computer-controlled 2D stage movement and z-axis actuation. The system automatically correlates spectral data with spatial coordinates without requiring manual intervention for each measurement point, enabling high-throughput operation.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If automated ambient ionization mass spectrometry imaging is used, then real-time in vivo analysis with high spatial resolution is achieved, but manual handling and sample preparation are reduced rather than eliminated

Engineering Contradiction:
Improvespatial resolutionVSAvoidmanual handling requirement
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces manual mechanical sampling with automated computer-controlled stage positioning and laser ablation. The 2D stage with high-precision z-axis actuator automatically positions the laser probe over tissue regions of interest, eliminating the need for manual tissue manipulation and sectioning while maintaining high spatial resolution through precise coordinate control.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 improves the accuracy and efficiency of tissue classification by allowing real-time, in vivo analysis with high spatial resolution and reduces the need for manual handling, enhancing the reliability of spectral libraries for multivariate classification models.

Implementation Method 1

ambient ionization techniques like laser ablation electrospray ionization

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Implementation Method 2

laser ablation electrospray ionization

Methodology Applied
Scientific EffectElectrospray ionization: Electrohydrodynamics

Implementation Method 3

The aerosol is then mixed with a matrix and aspirated into a vacuum chamber of a mass spectrometer and/or ion mobility spectrometer where it is caused to impact upon a collision surface causing the aerosol to be ionised by impact ionisation

Methodology Applied
Scientific EffectCharge transfer ionization: Ionisation

Data Source

PatentEP3726562B1Ambient ionization mass spectrometry imaging platform for direct mapping from bulk tissue
Publication Date: 2023.12.20 MICROMASS UK LTD
  • EP3726562B1 patent drawingFigure 1
  • EP3726562B1 patent drawingFigure 2
  • EP3726562B1 patent drawingFigure 3

AI summary

A method of ion imaging is disclosed that includes automatically sampling a plurality of different locations on a sample 20 using a first device 21 which is arranged and adapted to generate aerosol, smoke or vapour from the sample 20. Mass spectral data and/or ion mobility data corresponding to each location is obtained and the obtained mass spectral data and/or ion mobility data is used to construct, train or improve a sample classification model.