MALDI Imaging and Microscopy Co-Registration Without Post-Processing
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Solution Overview
Problem
Current methods for co-registering spatially resolved molecular and optical images in MALDI-MSI are inaccurate and time-consuming, especially for high-resolution imaging, due to systematic errors in pixel assignment and topography determination, leading to incomplete sample analysis and extended measurement times.
Innovation Solution
An apparatus and method that utilizes a desorption optics system for sample ionization, a transmission reflected light optics system for spatially resolved microscopy, and a computation unit to accurately associate molecular and optical image information, enabling precise co-registration and improved imaging quality.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If co-registration is performed using external markers and post-processing image corrections, then optical images can be aligned with mass spectrometry images, but systematic errors and artefacts occur leading to inexact co-registration
Solution Approach 1:
The patent merges the optical imaging system and mass spectrometry imaging system into a single integrated apparatus, allowing both modalities to capture images of the same sample area simultaneously or sequentially without requiring external markers or post-processing alignment. The computation unit directly associates the optical image data with the mass spectrometry image data based on their spatial correspondence, eliminating systematic errors from separate measurement and correction processes.
2Measurement precision
If high-resolution optical microscopy is used to define measurement ranges, then spatial precision is improved, but measurement times increase and sample areas are left unexamined due to safety margins
Solution Approach 1:
By integrating the optical imaging system with the mass spectrometry imaging system, the patent enables simultaneous or sequential acquisition of optical and molecular images of the same sample area without requiring safety margins. The computation unit directly associates the two data sets, allowing complete coverage of the sample area at high spatial precision without extending measurement times.
3Measurement precision
If multiple microscope images are used for co-registration with MALDI-MSI, then co-registration accuracy is improved, but the process becomes time-consuming and computation-intensive
Solution Approach 1:
The patent combines the optical imaging and mass spectrometry imaging into a single integrated system that captures both data types from the same sample area in the same coordinate system. The computation unit directly associates these data sets without requiring multiple microscope images or complex post-processing registration algorithms, significantly reducing processing time while maintaining high co-registration accuracy.
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
Achieves precise co-registration of molecular and optical images with sub-micrometer accuracy, allowing direct comparison of morphological and molecular information without shadowing, and reducing measurement time by eliminating the need for complex post-processing.
Implementation Method 1
a desorption optics system arranged and designed to subject sample material disposed on one side of a sample carrier to a first radiation and to bring about desorption of the sample material into the gas phase, with ionization of the desorbed sample material
Implementation Method 2
a transmission reflected light optics system arranged and designed to record light microscopy image information from the sample carrier and sample material in a spatially resolved manner using a second radiation in reflection through the transparent sample carrier
Implementation Method 3
an analyser disposed at a distance from the sample carrier and designed to receive the desorbed and ionized sample material and to process it to spatially resolved molecular image information
Data Source
AI summary
The invention relates to an apparatus for multimodal analysis of sample material, for example from a tissue, which detects molecular image information from the sample material in a spatially resolved manner, for example using a MALDI time-of-flight mass analyser, records light microscopy image information from the sample material in a spatially resolved manner, and associates the two with improved accuracy to give spatially resolved co-registered overall image information.