Biological Sample Image Alignment With Manual Glyph Refinement

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Solution Overview

Problem

Existing methods for spatial analysis of biological samples face challenges in accurately aligning images of biological samples with fiducial patterns and distinguishing sample regions from background, compounded by sample imperfections and handling issues, leading to inaccurate data alignment and increased background noise.

Innovation Solution

A system and method for aligning images of biological samples with fiducial patterns using glyph coordinates, allowing manual adjustment for precise alignment, and identifying sample regions through user input to reduce background noise and improve data resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If automated techniques are used to determine the reference frame of fiducials in images, then productivity is improved, but measurement precision deteriorates

Engineering Contradiction:
Improvealignment speedVSAvoidreference frame accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system performs preliminary automated alignment to establish an initial reference frame, then allows for subsequent manual refinement. This preliminary action captures the bulk of alignment tasks automatically while reserving the option for precision adjustments when needed.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The alignment system transitions from a static automated approach to a dynamic hybrid approach. The reference frame determination can operate in automated mode for routine cases and switch to manual adjustment mode when precision requirements demand it, making the system adaptable to different precision needs.

Inventive Principle:
Principle #15Dynamics

2Measurement precision

If manual adjustment of reference frame is performed, then measurement precision is improved, but loss of time increases

Engineering Contradiction:
Improvereference frame accuracyVSAvoidalignment time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The automated alignment system performs the initial reference frame determination without human intervention, serving itself for the routine alignment task. This eliminates the need for manual adjustment in cases where automated alignment suffices, saving time while maintaining adequate precision.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system provides feedback mechanisms that allow users to assess the quality of automated alignment results. If the automated reference frame determination meets precision requirements, no further action is needed. If not, the feedback triggers manual adjustment, ensuring precision is only improved when necessary.

Inventive Principle:
Principle #23Feedback

3Quantity of substance

If background regions are included in spatial analysis, then quantity of data is improved, but object-affected harmful factors increase

Engineering Contradiction:
Improvedata volumeVSAvoidbackground noise
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The system extracts and separates background regions from the biological sample regions in the image. By identifying and extracting the background portion, it can be excluded from subsequent spatial analysis, preventing background noise from contaminating the analyte data while preserving the integrity of the sample data.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Different regions of the image are assigned different qualities or statuses. The biological sample regions are marked for inclusion in analysis with high priority, while background regions are marked for exclusion. This local differentiation allows the system to process only relevant data, maintaining data quality while managing volume effectively.

Inventive Principle:
Principle #3Local quality

Data Source

PatentUS20250272996A1Systems and methods for evaluating biological samples
Publication Date: 2025.08.28 10X GENOMICS INC
  • US20250272996A1 patent drawing
  • US20250272996A1 patent drawing
  • US20250272996A1 patent drawing

AI summary

Systems and methods for evaluating a biological sample on a substrate are provided. An image of the biological sample and glyphs on the substrate are displayed on a display as a plurality of pixels. Respective indications are received of coordinates within the image of the glyph locations. These and a reference fiducial pattern that includes the plurality of glyphs are used to calculate and display an initial alignment between the image and the fiducial pattern. The alignment is updated through manual user adjustments to glyph coordinates. A set of pixels in the plurality of pixels depicting the biological sample are received from a user. Identification of each capture spot in a plurality of capture spots encompassed by the set of pixels is outputted to an output file, with each respective capture spot being identified within the image for the output file based on the updated alignment.