Electrophoretic Permeabilization for Spatially Resolved Analyte Capture

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Solution Overview

Problem

Existing methods for capturing analytes from biological samples fail to provide spatial information about the position of single cells within a tissue and often result in low analyte capture due to insufficient permeabilization, leading to loss of spatial resolution and increased diffusive migration.

Innovation Solution

An electrophoretic system is used to permeabilize biological samples, allowing analytes to migrate towards capture probes on a substrate by applying an electric field, thereby reducing diffusive migration and enhancing spatial resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional capture methods are used without sufficient permeabilization, then sample integrity is maintained, but analyte capture amount is too low for adequate analysis

Engineering Contradiction:
Improveanalyte capture amountVSAvoidpermeabilization process complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent replaces traditional chemical permeabilization methods with an electrophoretic system that uses electric fields to drive analyte migration. The electrophoresis device applies controlled voltage to move charged analytes from cells to capture probes, eliminating the need for complex chemical permeabilization protocols while achieving sufficient analyte release and capture.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If analytes are allowed to migrate to capture probes without active direction, then capture process is simple, but spatial resolution is lost due to diffusive migration

Engineering Contradiction:
Improvespatial resolutionVSAvoidelectrophoretic system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces passive diffusive migration with active electrophoretic migration driven by electric fields. The electrophoresis device applies controlled voltage to move charged analytes along defined paths from cells to capture probes, preventing lateral diffusion and maintaining spatial resolution while providing precise localization of captured analytes.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces an electric field as an intermediary to mediate analyte migration. The electrophoretic system uses electric fields to control the movement of charged analytes through the buffer solution, ensuring they migrate directly to capture probes rather than diffusing randomly, thus maintaining spatial information while facilitating capture.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If additional permeabilization processes are applied to increase analyte release, then analyte capture improves, but spatial resolution deteriorates and process complexity increases

Engineering Contradiction:
Improveanalyte capture amountVSAvoidspatial resolution
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent replaces additional chemical permeabilization steps with electrophoretic migration. The electrophoresis device efficiently extracts analytes from cells using electric field-driven migration, achieving high capture amounts without the need for repeated or intensified chemical permeabilization that would compromise spatial resolution and increase process complexity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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

The system improves spatial resolution by actively directing analytes to capture probes, increasing the amount of captured analytes and reducing the need for additional permeabilization processes, thus providing precise spatial location data.

Implementation Method 1

an electric field created by the electrophoretic system can cause analytes to be released from the cell, and effectively migrate toward and bind to the capture probes attached to the substrate

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 2

an electric field created by the electrophoretic system can cause analytes to be released from the cell, and effectively migrate toward and bind to the capture probes attached to the substrate

Methodology Applied
Scientific EffectElectric field: Electric Field

Data Source

PatentUS12405264B2Electrophoretic system and method for analyte capture
Publication Date: 2025.09.02 10X GENOMICS INC
  • US12405264B2 patent drawing
  • US12405264B2 patent drawing
  • US12405264B2 patent drawing

AI summary

An electrophoretic system is provided for analyte capture from a biological sample. The electrophoretic system can be used to permeabilize the sample to allow analytes to be released from the sample. For example, the sample can be contacted with capture probes attached to a substrate, and an electric field created by the electrophoretic system can cause analytes to be released from the cell, and effectively migrate toward and bind to the capture probes attached to the substrate.