High-throughput Mass Spectrometry Positioning via Internal Recognition Patterns
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Solution Overview
Problem
High-density sample arrays on sample support plates, especially those with monoatomic layers, become invisible under matrix coating, making it difficult to determine their precise position in mass spectrometers, leading to inaccurate characterization and reduced utilization of samples due to mechanical tolerances and limitations in visual recognition.
Innovation Solution
Incorporating finely structured internal position recognition patterns, such as crosses, during sample generation, which can be measured with high sensitivity and accuracy in the mass spectrometer to determine the precise position of each sample, allowing for precise scanning and characterization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high-density sample arrays with monoatomic layers are used, then sample quantity and density are improved, but visual recognition and position determination become impossible
Solution Approach 1:
The patent introduces matrix substance as an intermediary that enables detection of high-density samples. The matrix is applied in layers: first a base layer covering the entire array, then individual additional layers on each sample spot. This two-layer matrix approach makes the invisible monoatomic samples detectable by mass spectrometry while maintaining high density.
Solution Approach 2:
The patent creates visual copies of sample positions using fluorescent markers or dyes that are applied alongside the samples. These visual copies can be captured by video cameras to determine sample array positions, while the actual high-density samples remain intact for mass spectrometric analysis.
2Reliability
If matrix substance is added to achieve homogeneous coating, then ionization quality is improved, but sample position recognition is lost
Solution Approach 1:
The matrix coating is segmented into two distinct stages: a base layer applied uniformly across the entire sample array area, and individual additional layers applied to each specific sample spot. This segmentation allows the base layer to provide overall ionization capability while the additional layers maintain sample position visibility for recognition.
Solution Approach 2:
The base matrix layer is applied preliminarily before the samples are fully processed, creating a foundation for ionization. This preliminary action ensures that when individual sample spots receive additional matrix, the position recognition is already established and preserved.
3Ease of operation
If mechanical tolerances in sample support holders are present, then ease of operation is improved, but position reproduction accuracy deteriorates
Solution Approach 1:
The patent implements feedback mechanisms using video cameras to capture images of the sample array positions. These images provide feedback information that is processed to calculate precise position coordinates, which then guide the laser scanning process to compensate for mechanical tolerances in sample support holders.
Solution Approach 2:
The patent replaces reliance on mechanical precision with an optical measurement system. Instead of depending on mechanically precise sample support holders, the system uses video cameras and image processing to optically determine sample positions, substituting mechanical accuracy requirements with optical detection capabilities.
4Ease of operation
If video camera is used for position determination, then ease of operation is improved, but measurement capability is lost when samples are coated with matrix
Solution Approach 1:
The patent uses fluorescent markers or dyes as intermediary substances that are applied to sample positions. These intermediaries are visible to video cameras, enabling position determination. The markers serve as mediators between the invisible samples and the optical detection system, allowing camera-based positioning without interfering with mass spectrometric analysis.
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 precise determination of sample positions to within one to two micrometers, ensuring complete utilization of samples and accurate characterization, even at high densities, by using a mass spectrometer capable of generating small laser spots with high positional accuracy.
Implementation Method 1
ionization by matrix-assisted laser desorption (MALDI) with a narrowly focused laser beam in a mass spectrometer
Data Source
AI summary
The invention relates to the characterization of samples which are located in their many hundreds up to tens or hundreds of thousands on a sample support plate in a regular pattern, a so-called array, by ionization with matrix-assisted laser desorption and mass spectrometric measurement, for example. The invention proposes that the position of the sample pattern, and thus the position of each sample in the measuring instrument, for example a mass spectrometer, should be determined by measuring at least two finely structured internal position recognition patterns, such as fine crosses. The position recognition patterns are preferably applied as the samples are generated, with the same apparatus which also generates the sample pattern. A mass spectrometer in which laser spots with diameters of only four to five micrometers can be generated, which can preferably be positioned with an accuracy of one micrometer or better, is particularly suitable for the characterization.