Spatial Array Probe Blocking for Analyte Mislocalization

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Solution Overview

Problem

Existing methods for studying spatial heterogeneity in biological samples often result in analyte mislocalization, leading to decreased resolution, wasted resources, and inaccurate results due to non-specific binding of analytes to areas adjacent to the biological sample on spatial arrays.

Innovation Solution

The method involves blocking capture probes on a spatial array not directly under the biological sample by contacting them with a bulky moiety coupled to a blocking reagent, thereby inhibiting hybridization and reducing non-specific binding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If spatial array based technologies are used to study spatial heterogeneity, then analyte data can be obtained, but analytes mislocalize to areas adjacent to the biological sample causing decreased resolution and inaccurate results

Engineering Contradiction:
Improvespatial resolutionVSAvoidanalyte mislocalization
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by blocking capture probes in areas adjacent to the biological sample before analyte hybridization occurs. The blocking reagent is applied to prevent non-specific binding of analytes to capture probes outside the sample area, thereby preventing mislocalization before it happens and improving spatial resolution

Inventive Principle:
Principle #9Preliminary anti-action

Solution Approach 2:

The patent implements local quality by applying different treatments to different areas of the spatial array. The area adjacent to the biological sample receives a blocking reagent treatment, while the area under the biological sample remains active for analyte capture. This localized differentiation prevents mislocalization while preserving accurate spatial information

Inventive Principle:
Principle #3Local quality

2Reliability

If blocking reagents are applied to areas adjacent to the biological sample, then non-specific binding is reduced, but device complexity increases

Engineering Contradiction:
Improveaccuracy of spatial dataVSAvoidcomplexity of spatial array method
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses a blocking reagent as an intermediary substance that mediates between the capture probes and analytes in the adjacent areas. The blocking reagent specifically binds to capture probes in non-sample areas, preventing analyte mislocalization without interfering with the primary function of analyte capture under the biological sample

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies parameter changes by modifying the chemical state of capture probes in adjacent areas through blocking reagent treatment. This changes the binding affinity of these probes from high (capable of binding analytes) to low (blocked from binding), creating a chemical gradient across the array that improves accuracy

Inventive Principle:
Principle #35Parameter changes

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

This approach improves the efficiency and resource conservation of spatial analysis by reducing analyte mislocalization and non-specific binding, thereby enhancing the resolution and accuracy of spatial data.

Implementation Method 1

the capture probe in the first area hybridizes to the target analyte

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS20250179475A1Methods for reducing capture of analytes
Publication Date: 2025.06.05 10X GENOMICS INC
  • US20250179475A1 patent drawing
  • US20250179475A1 patent drawing
  • US20250179475A1 patent drawing

AI summary

Provided herein are methods, compositions, and kits for reducing capture of analytes from a biological sample on a spatial array on areas not covered by a biological sample.