Sample Holder Alignment for Calibrated Spatial Imaging
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Solution Overview
Problem
Existing imaging systems for spatial analyte data are variable in resolution and sensitivity due to manufacturer inconsistencies, apparatus differences, and user-dependent image acquisition, leading to inefficiencies and unpredictable results, especially in samples with unknown fluorescent intensity.
Innovation Solution
The use of control slides and substrates to assess image quality and resolution, featuring fiducial markers and fluorescent probes, allowing for pre-imaging calibration and alignment with barcoded areas, ensuring consistent heating, and reducing user error in spatial gene expression technologies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If imaging systems are used without control slides or calibration standards, then device complexity is reduced, but measurement precision deteriorates due to variability in resolution and sensitivity
Solution Approach 1:
The patent introduces control slides with fiducial markers and fluorescent probes as intermediary calibration standards between the imaging system and the actual biological samples. These control slides serve as mediators that enable consistent measurement and alignment without requiring complex adjustments to the imaging system itself, thereby improving measurement precision while avoiding increased device complexity.
2Reliability
If manual image acquisition procedures are used, then ease of operation is improved, but reliability deteriorates due to user-dependent variability
Solution Approach 1:
The patent implements preliminary calibration procedures using control slides with known fiducial markers and fluorescent probe concentrations. By performing alignment and quality assessment before actual sample imaging, the system establishes consistent reference parameters that reduce user-dependent variability. This preliminary action ensures reliability while maintaining ease of operation through standardized workflows.
3Productivity
If heating devices are used without proper thermal management, then productivity is improved, but temperature uniformity deteriorates causing condensation and protocol failure
Solution Approach 1:
The patent incorporates feedback mechanisms where control slides with temperature-sensitive indicators or fiducial markers provide real-time information about thermal uniformity during heating. This feedback allows the heating device to adjust its operation to maintain temperature uniformity across the substrate, preventing condensation and protocol failure while preserving heating efficiency and productivity.
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-calibration of imaging systems, reduces experimentation time, and ensures uniform heating and alignment, thereby improving image quality and reducing sample analysis costs.
Implementation Method 1
The array includes a plurality of non-metallic fluorescent markers, wherein a non-metallic fluorescent marker of the plurality of non-metallic fluorescent markers includes a fluorescent probe
Implementation Method 2
Other protocols involve temperature cycling and other steps in which the temperature of the sample is adjusted in controlled fashion. To heat the sample and its supporting substrate during a protocol, a thermocycler, heating plate, or other heating device may be used
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.