Correlated Chemical Mapping for Repeated Spatial Sample Analysis
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Solution Overview
Problem
Current mass spectrometry-based chemical imaging techniques face limitations due to the destructive nature of sampling and the limited time for analysis at each pixel or voxel, restricting the depth of chemical information that can be obtained and hindering the detection and quantification of low-abundance molecules.
Innovation Solution
A system and method for repeated analysis of samples at the same spatial location, utilizing a spectroscopic imager, sampling system, sample transfer unit, and data analysis system to obtain and process spatially-registered samples, allowing for multiple interrogations and enhanced chemical analysis, including mass spectrometry, with the ability to correlate results back to the original sample location.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If mass spectrometry-based chemical imaging uses destructive sampling at each pixel location, then spatial mapping of chemical distributions can be achieved, but the chemical content of each location can only be examined once, limiting the depth of chemical information
Solution Approach 1:
The patent segments the analysis process into two distinct stages: (1) non-destructive imaging acquisition that captures spatial distribution without consuming the sample, and (2) subsequent destructive analysis that can be performed multiple times on the same sample. This segmentation allows the sample to serve multiple analytical purposes, thereby increasing the depth of chemical information obtained while maintaining reliable repeated examination capability.
Solution Approach 2:
The patent performs preliminary non-destructive imaging acquisition before any destructive sampling occurs. By first obtaining spatial maps of chemical distributions using techniques like Raman imaging or infrared imaging, the system preserves the intact sample for subsequent repeated destructive analysis, ensuring that maximum chemical information can be extracted through multiple interrogations of the same location.
2Productivity
If mass spectrometry analysis is performed rapidly at each pixel location, then spatial mapping efficiency is improved, but the time available for detailed chemical analysis is extremely short, restricting detection sensitivity
Solution Approach 1:
The patent separates the imaging function from the detailed analysis function. Rapid non-destructive imaging (e.g., Raman or infrared imaging) quickly maps spatial distributions across the sample, while detailed mass spectrometry analysis is performed subsequently on selected regions or the entire sample. This segmentation allows high-speed spatial mapping without compromising the sensitivity of detailed chemical detection, as the latter can be performed with adequate time and resources.
Solution Approach 2:
The patent performs preliminary rapid imaging to identify regions of interest or establish spatial context before performing time-consuming, high-sensitivity mass spectrometry analysis. This preliminary action allows the system to efficiently guide subsequent detailed analysis, ensuring that detection sensitivity is maximized for relevant regions while maintaining overall productivity through selective sampling.
3Ease of operation
If ambient ionization techniques are used for sampling, then ease of sample preparation and flexibility are improved, but the ability to perform repeated analysis of the same location is limited
Solution Approach 1:
The patent segments the sampling and analysis processes by using ambient ionization techniques only for initial imaging and identification, while preserving the bulk sample for subsequent repeated analysis using more controlled sampling methods. This segmentation allows the system to benefit from the ease of ambient ionization for initial characterization while maintaining the ability to perform multiple analyses on the same sample location using techniques like laser capture microdissection or microsampling.
Solution Approach 2:
The patent introduces an intermediary step where ambient ionization imaging serves as a guide to identify and map chemical distributions, which then informs subsequent targeted sampling. This intermediary role allows the system to combine the advantages of ambient ionization (ease of operation, no vacuum required) with the advantages of controlled sampling methods (repeated analysis capability), as the ambient technique provides spatial guidance without consuming the sample.
Data Source
AI summary
A method for the repeated analysis of a sample bearing location. The sample bearing location may include, for instance, a sampled point in a tissue slice that is spatially and temporally correlated to the original slice. The slice may be in whole, or in part, a complete item or a portion of a complete item such as, for example, a human organ. The method improves the analysis process, such as mass spectrometry analysis, by providing a much more complete characterization of the target. The method also allows for the splitting of the sample and chemical/physical alteration of the aliquots for enhanced chemical analysis.