LAESI 3D Molecular Imaging of Live Tissue
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Solution Overview
Problem
Current methods for three-dimensional molecular imaging of live tissues or cells require extensive physical and chemical sample preparation, and are limited by the need for vacuum conditions, which prevents the study of live specimens and introduces artifacts such as post-mortem tissue degradation and analyte migration.
Innovation Solution
The combination of infrared laser ablation with electrospray ionization (LAESI) allows for three-dimensional molecular imaging of metabolites and other biomolecules in live tissues or cells without special preparation, performed at atmospheric pressure, using a focused IR laser beam to ablate a sample plume intercepted by charged electrospray droplets, which are then analyzed by mass spectrometry, enabling lateral scanning and depth profiling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If vacuum conditions are used for mass spectrometry imaging, then measurement precision is improved, but the specimen becomes damaged and loses viability
Solution Approach 1:
The patent applies atmospheric pressure environment instead of vacuum conditions, creating an inert-like atmosphere that preserves specimen viability while enabling mass spectrometry imaging. The electrospray ionization source operates at atmospheric pressure, eliminating the need for vacuum and thus preventing specimen damage and artifacts.
Solution Approach 2:
The patent replaces the vacuum-based mass spectrometry system with an atmospheric pressure electrospray ionization system. This substitution allows the ionization process to occur in air rather than vacuum, preserving live specimens while maintaining analytical capability through the electrospray ionization-mass spectrometry interface.
2Measurement precision
If extensive physical and chemical sample preparation is performed, then measurement precision is improved, but the analysis time increases and specimen artifacts are introduced
Solution Approach 1:
The electrospray ionization source performs self-ionization of analytes directly from the tissue surface without requiring external chemical reagents or extensive physical preparation. The charged spray droplets automatically ionize the molecules present, enabling direct analysis of fresh tissue sections with minimal processing.
Solution Approach 2:
The method requires only simple tissue sectioning and mounting on conductive substrates before analysis, performing the necessary preparation in advance without complex chemical treatments. This preliminary minimal preparation preserves molecular integrity while enabling rapid subsequent imaging.
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 provides high-resolution three-dimensional molecular distribution imaging of live tissues with minimal chemical and physical treatment, allowing for the direct analysis of metabolites, pharmaceuticals, and other biomolecules with resolutions of about 300-350 μm laterally and 30-40 μm in depth, correlating molecular distributions with their biological roles.
Implementation Method 1
A laser pulse at about 2.9 μm wavelength ablates a minute volume of the sample to eject fine neutral particles and/or molecules
Implementation Method 2
This laser plume is intercepted by an electrospray and the ablated material is efficiently ionized to produce mass spectra similar to direct electrospray ionization
Implementation Method 3
the ablated material is efficiently ionized to produce mass spectra similar to direct electrospray ionization
Data Source
AI summary
The field of the invention is atmospheric pressure mass spectrometry (MS), and more specifically a process and apparatus which combine infrared laser ablation with electrospray ionization (ESI).