Spatial Transcriptomics Array Resetting via Chemical Sample Removal
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Solution Overview
Problem
Current methods for studying spatial heterogeneity in tissues face challenges due to incorrect placement or damage of tissue samples on arrays, leading to compromised data quality and difficulty in resetting arrays without significant decreases in sequencing metrics.
Innovation Solution
A method for resetting arrays by identifying incorrect or damaged tissue samples and treating them with specific biological sample removal conditions, such as using potassium hydroxide or proteinase, to remove the sample without performing reverse transcription, allowing for reprocessing with new tissue without reducing sequencing metrics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If tissue sample is applied to array for spatial heterogeneity analysis, then gene expression data can be obtained, but incorrect placement or damage of tissue compromises data quality
Solution Approach 1:
The patent applies preliminary imaging and quality control measures before proceeding with reverse transcription. The array is imaged to verify correct tissue placement and integrity, and only after confirming acceptable quality does the protocol proceed to reverse transcription. This preliminary screening prevents compromised samples from affecting downstream sequencing metrics.
Solution Approach 2:
The patent enables selective removal of incorrectly placed or damaged tissue samples from the array before reverse transcription. By extracting only the problematic portions while leaving the array and capture probes intact, the system maintains the ability to reapply correct tissue samples without needing to discard the entire array, thus preserving data quality reliability.
2Adaptability or versatility
If array is reset by removing tissue sample, then new tissue can be reprocessed, but sequencing metrics decrease significantly
Solution Approach 1:
The patent performs preliminary verification that reverse transcription has not been performed before attempting to reset the array. This timing constraint ensures that the capture probes remain in their original state, ready for new tissue application. By establishing this preliminary condition, the system enables array resetting without compromising subsequent sequencing metrics.
Solution Approach 2:
The patent treats the tissue sample as a disposable component that can be removed without affecting the reusable array. The capture probes and array structure are designed to remain intact and functional after tissue removal, allowing the expensive array to be reused multiple times with different tissue samples while maintaining sequencing quality.
3Loss of information
If reverse transcription is performed on array, then analyte data can be captured, but array cannot be reset for new tissue
Solution Approach 1:
The patent establishes reverse transcription as a subsequent step that must occur after tissue application and quality verification, but before array resetting. This sequential arrangement ensures that the array can be reset for new tissue only after data capture is complete, preventing the need to choose between data capture and array reusability.
Solution Approach 2:
The patent segments the workflow into distinct phases: tissue application, quality imaging, optional resetting for reapplication, and finally reverse transcription. This segmentation allows flexible ordering where the array can be reset between tissue applications without interfering with the reverse transcription step, enabling both data capture and array versatility.
4Productivity
If tissue sample is removed from array, then array can be reused, but contamination from removed tissue may occur
Solution Approach 1:
The patent extracts and removes the tissue sample completely from the array surface using specific removal conditions before reapplication. This extraction process eliminates the risk of contamination from residual tissue while preserving the array structure and capture probes, enabling high-throughput reuse without contamination concerns.
Solution Approach 2:
The patent converts the potential harm of tissue residue into a benefit by using controlled removal conditions that selectively eliminate tissue while preserving array functionality. The removal process, which might otherwise risk damaging the array, is optimized to cleanly extract tissue without affecting the capture probes, turning a potential contamination issue into an opportunity for array reuse.
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 the removal of incorrectly placed or damaged tissue samples from arrays without compromising sequencing data quality, allowing for the reuse of arrays with new tissue samples, maintaining high sequencing metrics and minimizing contamination.
Implementation Method 1
a capture probe of the plurality of capture probes includes a capture domain that binds specifically to an analyte from the biological sample
Implementation Method 2
treating the array with a set of biological sample removal conditions, such that the biological sample is substantially removed from the array
Data Source
AI summary
Provided herein are methods for resetting an array to which a biological sample has been applied that include treating the array with a set of biological sample removal conditions.