Single-Probe MSI System for High-Resolution Single Cell Analysis
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Solution Overview
Problem
Current mass spectrometry imaging (MSI) techniques face limitations in spatial resolution, sensitivity, and sample preparation, particularly for biological samples, with methods like SIMS being restricted by high vacuum requirements and MALDI being time-consuming, while ambient desorption/ionization techniques like DESI and LAESI have issues with reproducibility and ion suppression.
Innovation Solution
A novel Single-probe MSI system integrates two capillaries into a single unit, allowing for direct coupling with a mass spectrometer and enabling high-resolution, non-destructive analysis of tissues and cells with reduced deadspace and improved ionization efficiency, facilitating the detection of analytes within single cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If SIMS is used for MSI, then spatial resolution can be achieved, but high vacuum requirements greatly limit application to biological systems
Solution Approach 1:
The patent introduces an ambient pressure ionization interface as an intermediary between the mass spectrometer and the biological sample. This interface allows ionization to occur at ambient pressure rather than requiring high vacuum, thereby enabling biological samples to be analyzed while maintaining the spatial resolution capabilities of MSI. The intermediary component bridges the gap between the vacuum-based MS detection and ambient pressure biological sampling.
2Productivity
If MALDI is used for MSI, then imaging capability is achieved, but surface treatment is obligatory and very time-consuming
Solution Approach 1:
The patent extracts the ionization function from the sample surface and relocates it to a separate ambient pressure ionization interface. By taking out the ionization step from the sample preparation process, the method eliminates the need for time-consuming surface treatment of the biological sample while preserving the imaging capability. The ionization occurs in the interface rather than requiring surface modification of the sample.
3Productivity
If DESI is used for ambient MSI, then rapid imaging measurement is achieved, but spatial resolution is relatively low and sensitivity is poor
Solution Approach 1:
The patent changes the operational parameters of the ionization process by operating at ambient pressure with optimized spray conditions and electric field parameters. This allows rapid imaging measurement to be maintained while improving spatial resolution and sensitivity through optimized ionization efficiency and reduced ion suppression effects that plague ambient pressure techniques.
4Productivity
If LAESI is used for ambient MSI, then rapid measurement is achieved, but the method is destructive and experiments are nearly non-reproducible
Solution Approach 1:
The patent replaces the mechanical laser ablation system with an ambient pressure ionization system that uses electrospray or similar non-destructive ionization methods. This substitution maintains rapid measurement capability while eliminating the destructive nature of laser ablation, thereby improving experiment reproducibility by preserving sample integrity for repeated measurements.
5Reliability
If nano-DESI is used for high resolution imaging, then non-destructive analysis is achieved, but fabrication of imaging probes and device operation are challenging
Solution Approach 1:
The patent creates a universal ambient pressure ionization interface that can be applied to various MSI configurations and sample types. This multi-functional interface simplifies device operation by providing a standardized platform that eliminates the need for complex custom probe fabrication, while maintaining non-destructive analysis capabilities through gentle ionization methods.
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 Single-probe MSI system enhances spatial resolution and sensitivity, enabling real-time, in situ analysis of single cells and tissues, overcoming limitations of existing techniques by providing high-resolution imaging and precise detection of analytes within cells.
Implementation Method 1
a first capillary tip (sampling tip) for sampling compounds within a single cell by inserting into the cell
Implementation Method 2
a second capillary tip (emitter tip) for ionizing the sampled species by nanospray electrospray ionization and delivering the ionized species to an inlet of a mass spectrometer
Data Source
AI summary
A sampling probe, system and analysis method is disclosed. The sampling probe in one embodiment is constructed of a silicon substrate having a first channel, a second channel, a first tapered tip with an opening, and a second tapered tip with an opening, wherein the first channel extends from the first tapered tip opening to the second tapered tip opening, and wherein the second channel extends from an inlet port to a junction with the first channel.