Spatial Barcoding With Transposases for Multi-Omic Profiling

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Solution Overview

Problem

Current spatial profiling methods are limited in their ability to simultaneously profile multiple types of biological molecules, such as DNA, open chromatin, chromatin features, proteins, and RNA, with high-throughput, single-molecule sensitivity, and spatial resolution, often suffering from issues like low efficiency, high cost, and imprecise spatial information.

Innovation Solution

A method using transposases to label biological molecules with detection probes, guided by light to assemble spatial barcodes, enabling high-throughput sequencing and spatial localization of various biological molecules, including DNA, open chromatin, chromatin features, and RNA, using a light microscope and standard tissue slides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If image-based methods are used for spatial profiling, then spatial resolution is improved, but time consumption increases and throughput decreases

Engineering Contradiction:

Improvespatial resolutionVSAvoidtime consumption

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces mechanical image-based detection with optical sequencing. Instead of using microscopes to image fluorescent signals, the invention uses optical fields to sequence DNA barcodes directly from spatial locations, eliminating the need for mechanical imaging systems and significantly reducing time consumption while maintaining spatial resolution

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from fluorescent signal intensity (image-based) to sequence information (genetic code-based). By encoding spatial information in DNA sequences rather than relying on fluorescent signal detection, the system achieves faster throughput without sacrificing spatial precision

Inventive Principle:

Principle #35Parameter changes

2Productivity

If multiple biological molecules are profiled simultaneously, then productivity is improved, but measurement precision deteriorates due to cross-contamination and background noise

Engineering Contradiction:

Improvemultiplexing capabilityVSAvoidspecificity of molecular identification

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the detection process by using distinct DNA barcodes for different biological molecules. Each molecule type is assigned a unique barcode sequence, allowing simultaneous profiling of multiple molecules while maintaining specificity through sequence discrimination rather than relying on separate detection channels that would cause cross-contamination

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces DNA barcodes as intermediary elements between the biological molecules and the detection system. These barcodes serve as mediators that carry spatial and molecular identity information, enabling simultaneous detection of multiple molecule types without direct interference between detection signals

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If high-throughput sequencing is used, then productivity is improved, but spatial information precision deteriorates

Engineering Contradiction:

ImprovethroughputVSAvoidspatial localization accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent merges spatial information with molecular identification in a single DNA barcode sequence. By combining location data and molecule type information into one encoded sequence, the system achieves high-throughput sequencing while maintaining precise spatial localization, as the barcode sequence directly reflects the spatial position where the molecule was detected

Inventive Principle:

Principle #5Merging (Combining)

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

Enables simultaneous quantification and spatial localization of multiple biological molecules with high-throughput sequencing, providing detailed spatial information at single-molecule sensitivity and lower cost, while reducing errors like off-target probe binding and background noise.

Implementation Method 1

using a transposase complex to label the biological molecule of interest with a detection probe

Methodology Applied

Scientific EffectTransposition:

Implementation Method 2

the detection probe comprises a photocleavable group; Illuminating a location of interest within the substrate to be spatially barcoded, wherein the illumination cleaves or alters the photocleavable group of the or each detection probe within the location

Methodology Applied

Scientific EffectPhotocleavable group cleavage: Photodissociation

Data Source

PatentUS20260071263A1Methods for spatial genomic, epigenomic and multi-omic profiling using transposases and light-activated spatial barcoding

Publication Date: 2026.03.12 CAMBRIDGE ENTERPRISE LTD

AI summary

The present invention relates to a method of spatially barcoding one or more biological molecules located on or within a substrate by using a transposase complex to label the biological molecule of interest with a detection probe which may then give rise to a spatial barcode. Such analysis may include determining the spatial profiling of one or more biological molecules, specifically the spatial analysis of DNA, open chromatin, chromatin features, proteins and/or RNA which may be spatially barcoded by methods of the invention, either alone or in various combinations. The invention further relates to a transposase complex for use in spatially barcoding one or more biological molecules and reagents kits for performing such methods.