Spatially Barcoded Surfaces with Photocleavable Bead Barcodes

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Solution Overview

Problem

Current spatial barcoding methods for studying cellular processes are complex, expensive, and lack sufficient resolution and convenience.

Innovation Solution

A method involving the use of beads with releasable barcode oligonucleotides, surface amplification, and diffusion inhibitors to create spatially barcoded surfaces, allowing for the formation of clonal populations and tandem barcode oligonucleotides to determine relative positions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current spatial barcoding methods are used, then spatial information can be recovered, but the technique complexity and expense increase

Engineering Contradiction:

Improvespatial resolutionVSAvoidtechnique complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The surface is divided into discrete bead locations, each serving as an independent spatial unit. Beads are distributed throughout the tissue section and each bead carries a unique barcode sequence, allowing the tissue to be segmented into resolvable units for spatial analysis

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The barcode sequences on beads are copied and amplified through PCR to generate sufficient signal for detection. The bead barcodes are used as templates for amplification, creating detectable copies that maintain the spatial information while enabling robust measurement

Inventive Principle:

Principle #26Copying

2Measurement precision

If current spatial barcoding methods are used, then molecular interactions can be analyzed, but the cost increases

Engineering Contradiction:

Improvespatial resolutionVSAvoidmanufacturing cost

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The method uses inexpensive fluorescent beads with synthetic barcode sequences attached via photocleavable linkers. These disposable beads can be easily synthesized and applied to surfaces, replacing expensive commercial spatial barcoding kits while maintaining analytical capability

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The barcode sequences are designed with photocleavable linkers that change from a bound state to a free state upon UV irradiation. This parameter change enables controlled release of barcodes from beads to capture oligonucleotides, simplifying the overall process

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If beads are closely spaced to increase resolution, then spatial information improves, but diffusion of molecules between beads increases

Engineering Contradiction:

Improvespatial resolutionVSAvoiddiffusion between beads

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

A gel matrix is introduced as an intermediary substance between the closely spaced beads. The gel acts as a diffusion barrier that prevents molecules from migrating between adjacent beads while still allowing the closely packed configuration to maintain high spatial resolution

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The harmful diffusion pathway is extracted and replaced by the gel matrix barrier. The gel removes the direct diffusion route between beads while maintaining the beneficial close spacing for resolution, effectively separating the conflicting requirements

Inventive Principle:

Principle #2Taking out (Extraction)

4Measurement precision

If barcode oligonucleotides are released and captured to form clonal populations, then measurement accuracy improves, but the process time increases

Engineering Contradiction:

Improvemeasurement accuracyVSAvoidprocess time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

Capture oligonucleotides are pre-attached to the surface before bead placement. This preliminary preparation ensures that when barcodes are released from beads, they can be immediately captured and amplified without requiring additional surface preparation steps, reducing overall process time while maintaining accuracy

Inventive Principle:

Principle #10Preliminary 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

Provides flexible, cost-effective spatially barcoded surfaces with improved resolution and convenience, enabling accurate determination of molecular indicators' positions on a surface.

Implementation Method 1

releasing the barcode oligonucleotides so that the barcode oligonucleotides are captured by capture oligonucleotides

Methodology Applied

Scientific EffectHybridization:

Implementation Method 2

surface amplifying the captured barcode oligonucleotides to form clonal populations of captured barcode oligonucleotides on the surface

Methodology Applied

Scientific EffectDNA amplification:

Implementation Method 3

adding to said surface a diffusion inhibitor that occupies interstitial spaces between said beads

Methodology Applied

Scientific EffectDiffusion barrier: Diffusion Barrier

Implementation Method 4

linked in the presence of a ligase to form a tandem barcode oligonucleotide

Methodology Applied

Scientific EffectLigation:

Data Source

PatentUS20250320542A1Spatially barcoded surfaces

Publication Date: 2025.10.16 CELLANOME INC

AI summary

The systems and methods described herein are directed to methods of making spatially barcoded surfaces by a spatially restricted release of unique oligonucleotide barcodes from beads.