Electrospray-Assisted Laser Desorption Ionization Mass Spectrometry
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Solution Overview
Problem
Current mass spectrometric imaging methods are inadequate for rapidly and accurately analyzing the spatial distribution of proteins in biological samples due to limitations in ionization, desorption, and precision, particularly under ambient conditions.
Innovation Solution
The method involves using electrospray-assisted laser desorption ionization mass spectrometry (ELDI-MS), where charge-laden liquid drops are directed towards a receiving unit, and a laser beam is scanned over the sample to desorb analytes, which are then occluded in the liquid drops to form ionized analytes, allowing for the construction of imaging profiles based on mass spectra.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If SIMS is used for imaging mass spectrometry, then detection of metal ions or small organic molecules is achieved, but macromolecules such as peptides or proteins cannot be detected because they are spoiled during ionization or cannot be effectively desorbed
Solution Approach 1:
The patent introduces an electrospray medium as an intermediary substance that facilitates the ionization and detection of macromolecules. The medium is sprayed onto the sample surface, allowing gentle ionization that preserves macromolecular integrity while enabling detection of peptides and proteins that cannot be detected by conventional SIMS methods.
Solution Approach 2:
The patent changes the ionization parameters by using electrospray ionization instead of direct SIMS ionization. This parameter change allows macromolecules to be ionized gently without being spoiled, expanding the detection capability to include peptides and proteins while maintaining their structural integrity.
2Reliability
If MALDI-MS is used for imaging, then peptide or protein molecules can be successfully desorbed from solid biological samples, but the method involves tedious preparation work and requires vacuum conditions
Solution Approach 1:
The electrospray-assisted laser desorption ionization system performs both the coating and ionization functions in an integrated manner under ambient conditions. The electrospray medium is automatically sprayed onto the sample surface and subsequently used for ionization during laser desorption, eliminating the need for separate matrix coating steps and vacuum requirements.
Solution Approach 2:
The patent replaces the vacuum environment requirement with ambient air operation. The electrospray system generates charged droplets that can be formed and directed in atmospheric pressure conditions, eliminating the need for vacuum chambers and complex preparation procedures associated with traditional MALDI-MS.
3Adaptability or versatility
If DESI-MS is used for direct protein mass spectrometric analysis, then a variety of compounds within a wide range of molecular weights can be studied, but there is difficulty in controlling the precision of striking electron-carrying spray droplets and inability to desorb protein molecules from the tissue slice
Solution Approach 1:
The patent applies preliminary action by first spraying the electrospray medium onto the sample surface before laser irradiation. This pre-coating step ensures that the sample surface is adequately prepared with ionization medium, allowing subsequent laser desorption to efficiently desorb protein molecules without the precision control problems of direct DESI spray striking.
Solution Approach 2:
The patent replaces the mechanical spray-direct-striking mechanism of DESI with a two-step process: electrospray coating followed by laser desorption. This substitution eliminates the need for precise mechanical positioning of spray droplets while maintaining the ability to study compounds across a wide molecular weight range, including proteins.
4Measurement precision
If conventional imaging mass spectrometry methods are used, then molecular distributions can be analyzed, but the analysis speed and accuracy are insufficient for rapid spatial analysis of proteins in biological samples
Solution Approach 1:
The patent implements continuous scanning of the laser beam across the sample surface combined with continuous electrospray medium delivery. This continuous action allows rapid acquisition of mass spectral data from multiple spatial locations, significantly increasing analysis speed while maintaining spatial distribution accuracy through systematic scanning patterns.
Solution Approach 2:
The patent uses periodic pulsing of the laser beam in conjunction with the continuous electrospray medium flow. The periodic laser pulses desorb ions at regular intervals from different spatial positions, allowing rapid buildup of spatially-resolved mass spectral data with high analysis speed and maintained precision through the periodic sampling scheme.
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 enables rapid, accurate, and unobstructive analysis of molecular distributions in solid biological samples, capable of detecting a wide range of molecules, including proteins, under ambient conditions, facilitating efficient molecular imaging.
Implementation Method 1
scanning a sample with a laser beam which has an irradiation energy sufficient to cause analytes contained in the sample to be desorbed to fly along a plurality of flying paths respectively
Implementation Method 2
permit a plurality of the analytes respectively along the plurality of flying paths to be occluded in a plurality of the charge-laden liquid drops respectively to thereby form a plurality of corresponding ionized analytes
Data Source
AI summary
A mass spectrometric imaging method includes the steps of: forcing sequentially generated charge-laden liquid drops to move towards a receiving unit of a mass spectrometer along a traveling path; scanning a sample with a laser beam which has an irradiation energy sufficient to cause analytes contained in the sample to be desorbed to fly along a plurality of flying paths respectively; and positioning the sample relative to the laser beam to render the plurality of flying paths intersecting the traveling path so as to permit a plurality of the analytes respectively along the plurality of flying paths to be occluded in a plurality of the charge-laden liquid drops respectively to thereby form a plurality of corresponding ionized analytes.