Barcode Probe Detection for Multiplexed Nucleic Acid Analysis

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Solution Overview

Problem

Current methods for detecting nucleic acids in biological samples lack accuracy, speed, and sensitivity, particularly in multiplexed detection, identification, and quantification.

Innovation Solution

A method involving probes with a target binding domain and a barcode domain, where the target binding domain recognizes and binds to a specific region of the nucleic acid, and the barcode domain uses multiple attachment regions with distinct sequences for sequential detection of detectable labels, allowing for accurate and sensitive multiplexed detection and quantification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional nucleic acid detection methods are used, then detection can be performed, but accuracy, speed, and sensitivity are insufficient particularly for multiplexed detection

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The probe is divided into distinct functional domains: a target binding domain for specific nucleic acid recognition and a barcode domain with multiple attachment regions for sequential label binding. This segmentation enables simultaneous optimization of detection accuracy through specific binding and detection speed through sequential label association.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The probe is pre-configured with multiple attachment regions in the barcode domain that can sequentially bind detectable labels. This preliminary structure allows rapid multiplexed detection by enabling sequential association of different labels without requiring separate probe preparations for each target.

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If conventional detection methods are used, then detection can be performed, but sensitivity is insufficient for multiplexed detection

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmethod complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

A single probe design with multiple attachment regions serves multiple detection functions simultaneously. The barcode domain can sequentially bind different detectable labels to detect multiple target nucleic acids in one assay, providing multi-functionality that enhances sensitivity without proportionally increasing method complexity.

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

Solution Approach 2:

The barcode domain acts as an intermediary structure between the target binding domain and detectable labels. This mediator enables sequential label binding to multiple attachment regions, amplifying the detection signal and enhancing sensitivity while maintaining a relatively simple overall method framework.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Adaptability or versatility

If multiple nucleic acids are detected simultaneously, then multiplexed detection is achieved, but the ability to identify specific regions is lost

Engineering Contradiction:
Improvemultiplexed detection capabilityVSAvoidspecific region identification
Core Design Contradiction:
Adaptability or versatilityVSLoss of information

Solution Approach 1:

Each attachment region in the barcode domain is assigned a distinct sequence that serves as a unique identifier for a specific target region. This local differentiation enables the system to maintain specific region identification capability while detecting multiple nucleic acids simultaneously through sequential label binding to different attachment regions.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The probe structure adds a temporal dimension to detection by enabling sequential binding of detectable labels to multiple attachment regions. This sequential process in time allows the system to resolve and identify specific target regions even when multiple nucleic acids are detected simultaneously in the same sample.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 rapid and sensitive detection and identification of multiple nucleic acids by sequentially ordering detectable labels associated with different attachment regions, enhancing the accuracy and efficiency of nucleic acid analysis.

Implementation Method 1

contacting the sample with at least one probe capable of recognizing and binding a first specific region of the at least one target molecule

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

binding to the first attachment region a first complementary nucleic acid molecule comprising a detectable label

Methodology Applied
Scientific EffectHybridization:

Implementation Method 3

a first complementary nucleic acid molecule of a first reporter complex comprising a detectable label

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP4324929B1Methods for detecting target nucleic acids in a sample
Publication Date: 2025.09.17 BRUKER SPATIAL BIOLOGY INC
  • EP4324929B1 patent drawingFigure 1
  • EP4324929B1 patent drawingFigure 2
  • EP4324929B1 patent drawingFigure 3

AI summary

The present invention provides probes, methods, kits, and apparatuses that provide accurate, rapid, and sensitive multiplexed detection, identification, and quantification of target nucleic acids in a sample.