Spatial Array Sample Holder Alignment for Multi-Analyte Capture
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Solution Overview
Problem
Existing imaging systems for spatial gene expression technologies lack efficient methods to assess image quality and resolution prior to sample analysis, leading to inefficiencies and potential experimental waste, especially when dealing with multiple fluorescent stains or samples with varied fluorescent intensities.
Innovation Solution
The use of control slides and substrates that include fiducial markers and arrays of non-metallic fluorescent markers to assess imaging system compatibility and optimize image acquisition parameters, along with devices that ensure even heating and alignment of substrates within heating devices, reducing user error and experimental costs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If imaging systems are used without control slides or calibration substrates, then the imaging process is simpler and faster, but image quality and resolution cannot be reliably assessed, leading to experimental waste
Solution Approach 1:
The patent applies preliminary action by implementing control slides and calibration substrates that contain fiducial markers and fluorescent markers arrays. These are prepared in advance to assess imaging system compatibility and optimize acquisition parameters before actual sample analysis, enabling pre-analysis quality assessment without adding complexity to the core imaging process
Solution Approach 2:
The patent uses control slides and calibration substrates as intermediary elements between the imaging system and the actual biological samples. These intermediaries contain fiducial markers for alignment and fluorescent markers for quality assessment, serving as a bridge to evaluate system performance before committing to experimental imaging
2Adaptability or versatility
If multiple fluorescent stains or samples with varied fluorescent intensities are analyzed, then more comprehensive spatial gene expression data is obtained, but image quality assessment becomes more difficult and experimental waste increases
Solution Approach 1:
The patent implements universality by designing control slides and calibration substrates that can assess imaging system performance across multiple fluorescent channels simultaneously. The fluorescent markers arrays contain markers with different intensities and spectral properties, enabling a single calibration process to validate the system's ability to handle varied fluorescent stains and intensities
Solution Approach 2:
The patent applies parameter changes by using fluorescent markers with varied intensities and spectral characteristics on the calibration substrates. This allows assessment of imaging system performance across different fluorescence parameters (intensity, wavelength, brightness), ensuring the system can reliably analyze multiple fluorescent stains with different properties
3Manufacturing precision
If substrates are not properly aligned or heated during processing, then the processing protocol is simpler, but spatial accuracy and data quality deteriorate
Solution Approach 1:
The patent implements feedback by using fiducial markers on substrates that provide reference points for alignment assessment. The imaging system captures images of these markers, and software algorithms calculate alignment accuracy and provide feedback for correction, enabling precise spatial alignment while maintaining ease of operation through automated measurement and correction guidance
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 efficient pre-analysis assessment of imaging systems, ensures uniform heating, and reduces experimental waste by allowing for precise alignment and calibration, thereby improving the quality and efficiency of spatial gene expression imaging.
Implementation Method 1
arrays of non-metallic fluorescent markers to assess imaging system compatibility
Implementation Method 2
devices that ensure even heating and alignment of substrates within heating devices
Data Source
AI summary
A sample holder includes a first member featuring a first retaining mechanism configured to retain a first substrate that includes a sample, a second member featuring a second retaining mechanism configured to retain a second substrate that includes a reagent medium, and an alignment mechanism connected to at least one of the first and second members, and configured to align the first and second members such that the sample contacts at least a portion of the reagent medium when the first and second members are aligned.