MALDI Matrix Micro-dot Array for Mass Spectrometry Imaging
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Solution Overview
Problem
Current MALDI-MS imaging techniques face issues with matrix deposition causing molecular diffusion, non-uniform crystallization defects, and sample depletion due to repeated laser firing, leading to unreliable mass data and images, especially in pathology samples.
Innovation Solution
Generating ions from a plurality of locations within a designated sample target site, rather than a single location, to average mass data and reduce the impact of defects and non-uniform matrix deposition, using a 'dithered' pattern to improve data reliability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Area of stationary object
If matrix is sprayed over the whole sample, then coverage is improved, but molecular diffusion occurs causing unreliable mass data
Solution Approach 1:
The patent segments the continuous matrix spray into discrete droplets that form separate micro-dots in an array. Each micro-dot is deposited at a specific location without overlapping with others, preventing molecular diffusion between regions while maintaining adequate coverage of the sample area.
Solution Approach 2:
The patent applies matrix with different properties at different locations by controlling droplet deposition. Each micro-dot receives a controlled amount of matrix material, creating locally optimized conditions for ionization while avoiding the diffusion problems associated with continuous spraying.
2Quantity of substance
If multiple laser shots are fired at the same sample target site, then ion generation is improved, but sample depletion occurs leading to reduced data quality
Solution Approach 1:
The patent segments the laser irradiation process by directing multiple laser shots at different micro-dots within the same sample region. This distributes the sample consumption across multiple locations, preventing depletion at any single target site while maintaining adequate ion generation from each location.
Solution Approach 2:
The patent transitions from a single-point laser target to a multi-point array of micro-dots. By distributing laser shots across multiple spatial locations (adding spatial dimensionality), the system maintains ion generation efficiency while avoiding sample depletion that occurs with repeated shots at a single location.
3Reliability
If matrix is deposited as tiny droplets in discrete regions, then molecular diffusion is reduced, but non-uniform crystallization defects occur
Solution Approach 1:
The patent accepts and works with the local variations in crystallization that result from droplet deposition. Each micro-dot develops its own crystallization pattern, and the system is designed to sample multiple locations to average out these local variations, rather than requiring perfect uniformity across the entire sample.
Solution Approach 2:
The patent segments the sampling process to acquire mass data from multiple micro-dots rather than relying on a single large matrix region. This segmentation allows the system to average out crystallization defects across multiple locations, achieving reliable data despite non-uniform crystallization at individual sites.
4Measurement precision
If data is acquired from multiple sample target sites, then signal-to-noise ratio is improved, but measurement time increases
Solution Approach 1:
The patent segments the sample into an array of micro-dots that can be rapidly scanned by the laser. This segmentation enables parallel processing of multiple locations, improving signal-to-noise ratio through data averaging while minimizing the time penalty through efficient sequential acquisition.
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 enhances the reliability and accuracy of mass data and images by averaging data from multiple locations within each sample target site, reducing the effects of defects and sample depletion, resulting in more consistent and reliable composition data for tissue samples.
Implementation Method 1
firing a laser beam at the sample to generate ions
Implementation Method 2
generate ions for analysis by mass spectrometry
Implementation Method 3
the matrix is a comparatively low molecular weight organic compound that readily absorbs light at the wavelength of the laser
Implementation Method 4
the matrix is applied on top of the sample, such that the matrix material permeates into the sample and crystallises in-situ
Data Source
AI summary
The present invention provides a method of generating ions from a sample, the method comprising the steps of (1) designating a plurality of sample target sites, and (2) for each of said plurality of sample target sites, generating ions from a plurality of locations associated with the sample target site, wherein said plurality of locations are selected automatically with reference to the said sample target site. Each of the plurality of sample target sites is associated with a discrete sample region, wherein the sample is part of a MALDI ion source and the plurality of discrete sample regions comprise regions of matrix, suitably formed by chemical inkjet printing. The plurality of locations can be at least 5 and preferably at least 10 locations, each of which can be selected randomly or in accordance with a predetermined pattern. Ions generated from the plurality of locations associated with each of the sample target sites are assigned only a single set of sample position coordinates, which coordinates correspond to those of the sample target site. This averaging technique leads to improved data reliability.