Barcoded Nucleic Acid Enrichment for Equal Pooled Screening

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing methods for nucleic acid sample enrichment, particularly in low fetal fraction samples, are inefficient and fail to maintain sample origin identification when pooling samples, leading to unequal representation and reduced sensitivity and specificity in genetic screening assays.

Innovation Solution

A method involving the use of sequence-based barcodes to label nucleic acid fragments from individual samples, followed by pooling and adjusting volumes based on calculated numerical offsets to ensure equal representation of target nucleic acid fractions, allowing for enrichment and maintaining sample origin identification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If samples are pooled for enrichment, then productivity is improved, but sample origin identification is lost

Engineering Contradiction:

Improvethroughput of enrichment processVSAvoidsample origin identification

Core Design Contradiction:

ProductivityVSLoss of information

Solution Approach 1:

The patent uses sequence-based barcodes as informational copies that tag each nucleic acid fragment with its sample origin. These barcodes are incorporated into the nucleic acid sequences themselves, allowing the original sample identity to be preserved and tracked throughout the pooling and enrichment process without preventing sample mixing.

Inventive Principle:

Principle #26Copying

2Loss of time

If samples are pooled for enrichment, then loss of time is reduced, but manufacturing precision deteriorates due to unequal representation

Engineering Contradiction:

Improvetime for individual sample processingVSAvoidequality of sample representation

Core Design Contradiction:

Loss of timeVSManufacturing precision

Solution Approach 1:

The patent implements a feedback mechanism where the sequence-based barcodes are used to quantify and track the representation of each sample in the pooled enrichment. This allows for measurement of enrichment outcomes per sample and adjustment of input amounts to achieve equal representation, ensuring precision is maintained despite parallel processing.

Inventive Principle:

Principle #23Feedback

3Measurement precision

If fetal fraction is increased through enrichment, then sensitivity is improved, but device complexity increases

Engineering Contradiction:

Improvesensitivity of genetic screeningVSAvoidcomplexity of enrichment methodology

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces sequence-based barcodes as an intermediary element that facilitates the enrichment process. These barcodes serve as mediators that allow for targeted enrichment of specific samples or sample types (e.g., fetal DNA) within the pooled mixture, enabling sensitive detection without requiring complex physical separation or purification methods.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP4153777B1Nucleic acid sample enrichment and screening methods

Publication Date: 2026.02.11 MYRIAD WOMENS HEALTH INC

Figure 1
Figure 2
Figure 3

AI summary

Described herein are methods for enriching test samples for target nucleic acid molecules for further genetic screening. Methods may comprise isolating nucleic acid from test subjects, preparing nucleic acid libraries wherein the nucleic acid molecules are tagged or barcoded to identify sample of origin, determining fragment size distribution, determining abundance of a target nucleic acid population, calculating numerical offset values to determine amount of libraries to add for fragment size selection, performing fragment size selection, and performing a diagnostic assay on a sample enriched for a target nucleic acid.