Multi-Stage Ionization for High Resolution Mass Spectrometry
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Solution Overview
Problem
Current mass spectrometry techniques, such as MALDI and SIMS, face challenges in achieving high spatial resolution for sub-cellular analysis due to fragmentation and matrix interference, limiting their ability to analyze small samples without disrupting molecular structures or causing migration.
Innovation Solution
A multi-stage ionization system that decouples desorption and ionization, using a primary beam to desorb neutral molecules without ionization in the first stage, followed by radiofrequency ionization in the second stage, allowing for nano-meter resolution and direct analysis without matrix application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If MALDI imaging is used to analyze tissue samples, then molecular identification is improved, but spatial resolution deteriorates due to large laser spot size
Solution Approach 1:
The patent segments the ionization process into two distinct stages: desorption of neutral molecules followed by separate ionization. This segmentation allows the use of a focused primary ion beam for desorption (achieving high spatial resolution) while using a broader ionization field for efficient molecular ionization (maintaining molecular identification accuracy).
Solution Approach 2:
The patent introduces an intermediary step where neutral molecules are first desorbed from the sample surface by a focused primary ion beam, then these neutral molecules are ionized in a separate stage. This intermediary desorption step acts as a mediator that enables both high spatial resolution (through focused beam) and efficient ionization (through subsequent ionization stage).
2Length of moving object
If SIMS imaging is used to achieve high spatial resolution, then nanometer resolution is improved, but molecular structure integrity deteriorates due to hard ionization fragmentation
Solution Approach 1:
The patent divides the ionization process into two separate stages: a desorption stage using a focused primary ion beam for high spatial resolution, and a separate ionization stage. This segmentation allows soft desorption of intact molecules while maintaining nanometer-scale spatial resolution, avoiding the fragmentation problem of conventional SIMS.
Solution Approach 2:
The patent changes the energy parameters of the ion beam by using a lower energy primary ion beam for desorption compared to conventional SIMS, and then applies a separate ionization field in the second stage. This parameter change enables gentle desorption that preserves molecular integrity while achieving high spatial resolution.
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
Enables soft desorption and ionization with increased spatial resolving power, minimizing fragmentation and contamination, and providing intact molecular analysis for peptides and proteins at the cellular level.
Implementation Method 1
a desorption beam configured to desorb neutral molecules from a target of a material
Implementation Method 2
a ionization source configured to ionize at least a portion of the neutral molecules after desorption from the target of the material, the ionization source being a radiofrequency ionization ('RFI') source
Data Source
AI summary
The present disclosure provides a system and method for mass spectrometry imaging in a multi-stage ionization applying different technologies by decoupling the desorption and ionization events. At a first stage, a primary beam, such as an ion beam, desorbs one or more molecules of a targeted sample, and at a second stage the desorbed molecules are ionized. The system and method can act independent of a matrix application to the target sample for a direct analysis and has the spatial resolution needed to operate in nano-meters resolution for a cell-by-cell analysis, if desired. The first stage desorption applies a first technique that allows neutral molecules of the target sample to become desorbed from the surface without requiring the molecules to be ionized during the desorption. The second stage ionizes the neutral molecules after the desorption in the first stage, when the defined target molecules have been volatilized.