Laser Ionization Mass Cytometry for Higher Sensitivity
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Solution Overview
Problem
Current mass spectrometry techniques, such as those using inductively coupled plasma (ICP), face limitations in ionization efficiency and sensitivity, particularly when analyzing biological samples, due to space charge effects and interference from carrier gas ions.
Innovation Solution
The use of a laser ionization system, which employs a pulsed laser to ionize sample material directly, reducing the introduction of carrier gas ions and enhancing ionization efficiency, particularly suitable for mass cytometry and imaging mass spectrometry applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If inductively coupled plasma (ICP) is used for ionization, then ionization capability is achieved, but ionization efficiency and sensitivity deteriorate due to space charge effects and carrier gas ion interference
Solution Approach 1:
The patent extracts and removes the harmful carrier gas ions from the ionization process by replacing ICP with direct laser ionization. The laser ionizes only the sample material directly, eliminating the introduction of carrier gas ions that cause space charge effects, thereby improving sensitivity and reducing interference
Solution Approach 2:
The patent replaces the thermal/mechanical ICP ionization system with an optical laser ionization system. The laser directly ionizes sample material through photonic energy, substituting the complex plasma generation mechanism with a more precise optical ionization process that avoids carrier gas interference
2Adaptability or versatility
If multiple fluorescent labels are used, then measurement capability is enhanced, but spectral overlap increases causing misassignment of detected emission
Solution Approach 1:
The patent changes the detection parameter from optical wavelength (fluorescence) to mass-to-charge ratio (mass spectrometry). Each metal isotope has a unique mass, allowing precise discrimination of multiple labels simultaneously without spectral overlap, thereby maintaining versatility while improving measurement precision
3Ease of operation
If carrier gas is used in mass spectrometry, then ion transport is facilitated, but sensitivity deteriorates due to introduction of carrier gas ions
Solution Approach 1:
The patent removes the carrier gas component from the ionization process by using direct laser ionization in a vacuum or reduced pressure environment. This extraction of carrier gas eliminates the source of interfering ions while maintaining ion transport capability through the mass spectrometer
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
The laser ionization system improves the sensitivity and specificity of mass spectrometry analysis by minimizing space charge effects and increasing the number of detectable ions, enabling more precise characterization of biological samples at the cellular and subcellular level.
Implementation Method 1
a laser ionisation system to receive material from the sampler, wherein the laser ionisation system comprises an ionisation system conduit and a pulsed laser adapted to ionise sample material passing through or exiting the ionisation system conduit
Data Source
AI summary
Embodiments of the present invention relate to replacement of the previous ICP-based ionisation system with a new laser ionisation system, providing improved mass spectrometer-based apparatus and methods for using them to analyse samples, in particular the use of mass spectrometry mass cytometry, imaging mass spectrometry and imaging mass cytometry, for the analysis of biological samples. Accordingly, embodiments of the present invention provide an apparatus, for example a mass cytometer, comprising: 1) a sampler; 2) a laser ionisation system to receive material removed from the sample by the sampler, wherein the laser ionisation system comprises an ionisation system conduit and a pulsed laser adapted to ionise sample material passing through or exiting the ionisation system conduit; and 3) a mass spectrometer to receive elemental ions from said ionisation system and to analyse said elemental ions.