Spatial Arrays with Capture Probe Release Mechanisms

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Solution Overview

Problem

Existing methods for determining the spatial location of analytes in biological samples are limited by their inability to provide comprehensive data on analyte position within intact tissues, and they often require expensive consumables and sequencing costs.

Innovation Solution

The use of spatial arrays with capture probes having different release mechanisms, such as restriction sites, cleavage domains, and photocleavable domains, allows for the reuse or multiplexed use of the array, enabling the capture of multiple analytes from the same or different biological samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If spatial arrays with capture probes are used to determine spatial location of analytes, then measurement precision is improved, but loss of substance increases due to single-use consumables

Engineering Contradiction:
Improvespatial location determinationVSAvoidconsumables
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The patent implements capture probe release mechanisms that enable the recovery and reuse of capture probes from spatial arrays. After analyte capture and detection, the release mechanisms (enzymatic cleavage, chemical bonds, physical detachment) allow capture probes to be removed from the array, purified, and reused for subsequent experiments, directly reducing consumable loss while maintaining spatial location measurement precision

Inventive Principle:
Principle #34Discarding and recovering

Solution Approach 2:

The spatial array system is designed with universal capture probes that can be released and reused across multiple experimental conditions and analyte types. The array platform and probe release mechanisms are engineered to support repeated use without compromising measurement precision, allowing a single array to serve multiple detection purposes

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If spatial arrays are designed for high measurement precision, then device complexity increases due to multiple capture probe sets

Engineering Contradiction:
Improvespatial location determinationVSAvoidarray structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent divides the capture probe population into multiple distinct sets, each with specific release mechanisms or capture specificities. This segmentation allows precise control over which probes are released under different conditions, enabling complex spatial measurements without requiring all probes to be permanently attached or irreversibly bound

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The spatial array incorporates dynamic release mechanisms that allow capture probes to transition from a bound state to a released state based on experimental conditions. This dynamic control enables the same array structure to adapt to different measurement requirements, reducing the need for multiple fixed complex array designs

Inventive Principle:
Principle #15Dynamics

3Productivity

If multiple analytes are captured from the same sample, then productivity increases, but device complexity increases due to probe release mechanisms

Engineering Contradiction:
Improveanalyte capture throughputVSAvoidrelease mechanisms
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent enables sequential capture of multiple analyte types from the same biological sample by releasing and replacing capture probe sets between measurements. After capturing analyte set A, the probes are released, the array is prepared for analyte set B, thereby multiplying the productivity of a single array without requiring permanently complex multi-analyte probe designs

Inventive Principle:
Principle #34Discarding and recovering

Solution Approach 2:

The system employs periodic cycles of capture and release operations on the spatial array. Each cycle captures a specific analyte set, then releases the probes for replacement or reuse. This periodic operation pattern enables high productivity across multiple analyte measurements while keeping the array structure relatively simple during each individual capture event

Inventive Principle:
Principle #19Periodic action

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 allows for the determination of the spatial location of analytes in biological samples with improved efficiency and reduced costs, by enabling the reuse of spatial arrays and capturing multiple analytes from various samples.

Implementation Method 1

contacting the array with a restriction endonuclease to release the first set of capture probes from the array

Methodology Applied
Scientific EffectRestriction endonuclease cleavage: Enzyme

Implementation Method 2

exposing the array to light to release the first set of capture probes from the array

Methodology Applied
Scientific EffectPhotocleavage: Photodissociation

Data Source

PatentUS20250075261A1Spatial arrays containing capture probes with different release mechanisms
Publication Date: 2025.03.06 10X GENOMICS INC
  • US20250075261A1 patent drawing
  • US20250075261A1 patent drawing
  • US20250075261A1 patent drawing

AI summary

The present disclosure features methods, composition, and kits including spatial arrays including capture probes with two or more different release mechanisms.