Vacuum Nanospray Specimen Imaging for Low-Fragmentation Mapping
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Solution Overview
Problem
Current specimen imaging methods, such as SIMS and DESI, face limitations in spatial resolution, fragmentation, and pretreatment steps, making it difficult to achieve high-resolution topological and chemical mapping of specimens, especially in biological samples.
Innovation Solution
A specimen imaging system combining an electron beam generator, a nanospray dispenser, and a mass spectrometer in a vacuum environment, where the electron beam is used for topological imaging and the nanospray for desorption and charging, allowing for sub-micron resolution and reduced fragmentation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If SIMS is used for imaging, then spatial resolution is improved (50 nm), but fragmentation increases and specimen integrity deteriorates
Solution Approach 1:
The patent changes the ionization method from high-energy ion beam sputtering (SIMS) to low-energy electrospray ionization, operating at atmospheric pressure instead of vacuum. This parameter change reduces fragmentation while achieving comparable spatial resolution through a different physical mechanism that is gentler on biological specimens
Solution Approach 2:
The patent replaces the mechanical ion beam sputtering system with an electrospray ionization system that uses charged droplets. This substitution eliminates the harsh mechanical bombardment that causes fragmentation while maintaining the ability to achieve high spatial resolution through controlled droplet deposition
2Object-generated harmful factors
If DESI is used for imaging, then specimen integrity is maintained, but spatial resolution deteriorates (10 μm)
Solution Approach 1:
The patent applies local quality by using a focused electrospray tip that delivers charged droplets to a localized region (50-500 μm from the substrate). This localized application allows the gentle desorption of DESI to achieve higher spatial resolution by concentrating the ionization effect in a smaller area rather than diffuse atmospheric spraying
3Manufacturing precision
If MALDI is used for imaging, then spatial resolution is improved, but pretreatment complexity increases
Solution Approach 1:
The patent extracts the matrix application step from the imaging process by using direct electrospray ionization of the specimen without requiring a matrix coating. This eliminates the complex pretreatment steps of matrix crystallization and optimization while achieving comparable or better spatial resolution through direct ionization of endogenous molecules
Solution Approach 2:
The electrospray system performs self-service by automatically ionizing and desorbing molecules from the specimen surface without requiring external matrix assistance. The charged droplets from the electrospray tip directly interact with the specimen, eliminating the need for separate matrix application, crystallization, and optimization steps
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 system achieves improved spatial resolution of up to 10 μm or less, with reduced fragmentation and fewer pretreatment steps, enabling detailed topological and chemical mapping of specimens while maintaining specimen integrity.
Implementation Method 1
an electron beam generator configured to generate an electron beam and focus the electron beam on a first predetermined location on the specimen
Implementation Method 2
a nanospray dispenser configured to dispense a nanospray onto a second predetermined location on the specimen, wherein the nanospray contacts the specimen as a charged, continuous liquid filament or as a plurality of charged droplets
Data Source
AI summary
Specimen imaging systems and methods including a sample stage in a vacuum environment. The sample stage is configured to support a specimen, an electron beam generator configured to focus an electron beam on a first predetermined location on the specimen, a nanospray dispenser configured to dispense a nanospray onto a second predetermined location on the specimen, a mass spectrometer, and an extraction conduit configured to extract a plume of charged particles generated as a result of contact between the nanospray and the specimen and deliver the charged particles to the mass spectrometer. The systems and methods can create a topological and chemical map of the specimen by analyzing at least a portion of the specimen with a mass spectrometer to determine a chemical composition of the specimen at the second predetermined location and analyzing at least a portion of the specimen with the electron beam to determine a surface topology.