Barcoded Beads for Nucleic Acid Sequencing

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Solution Overview

Problem

Current genomic sequencing methods face challenges in efficiently processing and identifying nucleic acid samples, particularly in diagnostics, prognostics, and forensic biology applications.

Innovation Solution

The development of methods and compositions for generating beads with covalently attached polynucleotides, enabling polynucleotide barcoding through the attachment of nucleic acid barcode molecules to polynucleotides, and subsequent pooling and partitioning to create diverse barcode sequences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional genomic sequencing methods are used, then basic sequencing can be performed, but efficient processing and identification of nucleic acid samples is challenging

Engineering Contradiction:
Improvesample processing efficiencyVSAvoidsequencing system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent segments the sequencing process into distinct functional stages: sample partitioning into separate reaction chambers, barcode assignment to identify sample origins, and pooled sequencing. This segmentation enables parallel processing of multiple samples simultaneously, dramatically improving throughput while maintaining manageable complexity through modularization of each stage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces barcode molecules as intermediary elements that carry identification information about sample origins. These barcodes are attached to nucleic acid samples and remain throughout the sequencing process, enabling efficient sample tracking and identification without requiring complex real-time monitoring systems, thus resolving the contradiction between processing efficiency and system complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If multiple samples are processed simultaneously, then productivity increases, but sample identification and tracking becomes more difficult

Engineering Contradiction:
ImprovethroughputVSAvoidsample origin identification
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent applies preliminary action by assigning unique barcodes to samples before pooling them for sequencing. The barcode attachment occurs in advance, allowing samples to be pre-identified and tracked throughout the sequencing process. This preliminary tagging enables simultaneous processing of multiple samples while maintaining complete identification records, eliminating the trade-off between throughput and sample tracking.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If nucleic acid barcoding is implemented, then sample identification improves, but additional processing steps are required

Engineering Contradiction:
Improvesample identification accuracyVSAvoidprocessing workflow complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the barcode attachment step with existing sample preparation procedures, combining identification tagging with nucleic acid extraction or amplification steps. By integrating barcode assignment into the existing workflow rather than adding it as a separate sequential step, the patent improves sample identification accuracy without proportionally increasing processing complexity.

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

This approach allows for efficient sample processing and identification by enabling the use of barcoded beads for nucleic acid analysis, facilitating advanced sequencing and characterization of nucleic acid samples.

Implementation Method 1

beads with covalently attached polynucleotides

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentUS20250027149A1Methods and systems for processing polynucleotides
Publication Date: 2025.01.23 10X GENOMICS INC
  • US20250027149A1 patent drawing
  • US20250027149A1 patent drawing
  • US20250027149A1 patent drawing

AI summary

This disclosure provides methods and compositions for sample processing, particularly for sequencing applications. Included within this disclosure are bead compositions, such as diverse libraries of beads attached to large numbers of oligonucleotides containing barcodes. Often, the beads provides herein are degradable. For example, they may contain disulfide bonds that are susceptible to reducing agents. The methods provided herein include methods of making libraries of barcoded beads as well as methods of combining the beads with a sample, such as by using a microfluidic device.