Capillary Collimation for Laser Ablation Electrospray Ionization
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Solution Overview
Problem
Conventional mass spectrometry techniques face challenges in efficiently analyzing small sample volumes and subcellular components due to low ionization efficiency, sensitivity, and detection limits, often causing perturbations in biological samples and requiring complex sample preparation.
Innovation Solution
The implementation of a collimated ablation plume in laser ablation electrospray ionization (LAESI) mass spectrometry, where a capillary or hollow waveguide is used to confine and direct the ablation plume, enhancing ionization efficiency and sensitivity by minimizing radial expansion and optimizing plume dynamics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional mass spectrometry techniques are used for analyzing single cells and subcellular components, then sample preparation can be performed, but the analysis time increases and molecular composition may be altered
Solution Approach 1:
The patent extracts and eliminates the matrix component from the analysis system. By using laser ablation to directly ionize samples without a matrix, the method removes the source of spectral interference and simplifies the analysis process, achieving both high precision and reduced analysis time
Solution Approach 2:
The laser ablation electrospray ionization source serves multiple functions simultaneously: it performs ablation, ionization, and direct introduction of ions to the mass analyzer. This multi-functionality eliminates the need for separate sample preparation steps, reducing analysis time while maintaining measurement precision
2Reliability
If matrix-assisted laser desorption ionization (MALDI) is used, then ionization can be achieved, but matrix interference occurs and sample preparation becomes complex
Solution Approach 1:
The patent removes the matrix component entirely from the ionization process. By using direct laser ablation electrospray ionization, the method achieves reliable ionization without matrix interference, eliminating the need for complex matrix application and sample preparation steps
Solution Approach 2:
The patent introduces an electrospray intermediary between laser ablation and mass analysis. The electrospray plume serves as a mediator that captures ablated material and facilitates ionization in a controlled manner, achieving reliable ionization without requiring matrix assistance
3Productivity
If organic solvents are used in direct organelle mass spectrometry, then analysis can be performed, but interference with single cell and subcellular component analysis occurs
Solution Approach 1:
The patent creates an inert analysis environment by using water-based electrospray solutions instead of organic solvents. This inert environment prevents interference with labile biological molecules while maintaining high analysis throughput through direct ionization of ablated material
4Measurement precision
If capillary electrophoresis is combined with mass spectrometry for separation, then separation can be achieved, but analysis time and complexity increase
Solution Approach 1:
The patent extracts and removes the capillary electrophoresis separation step from the analytical workflow. By using direct laser ablation electrospray ionization, the method achieves sufficient separation through the ablation process itself, eliminating the need for additional separation equipment and reducing system complexity while maintaining measurement precision
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 in vivo analysis of single cells and subcellular components with minimal sample preparation, improving ion formation, detection limits, and throughput, enabling simultaneous detection of multiple components and reduced sample manipulation.
Implementation Method 1
a laser system to emit a laser pulse to ablate the sample and generate an ablation plume
Implementation Method 2
The capillary may collimate an ablation plume generated in the capillary. The capillary may reduce and/or eliminate radial expansion of the ablation plume.
Implementation Method 3
an electrospray apparatus to generate an electrospray plume to intercept the ablation plume to produce ions
Implementation Method 4
a mass spectrometer having an ion transfer inlet to capture the ions
Data Source
AI summary
In various embodiments, a device may generally comprise a capillary having a first end and a second end; a laser to emit energy at a sample in the capillary to ablate the sample and generate an ablation plume in the capillary; an electrospray apparatus to generate an electrospray plume to intercept the ablation plume to produce ions; and a mass spectrometer having an ion transfer inlet to capture the ions. The ablation plume may comprise a collimated ablation plume. The device may comprise a flow cytometer. Methods of making and using the same are also described.