Cell Labeling With Nucleic Acid Barcodes for Parallel Analysis

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Solution Overview

Problem

Current sample processing techniques are limited by the inability to process multiple biological samples in parallel, particularly in high-throughput applications such as single-cell analysis, due to the lack of efficient methods for partitioning and identifying cells within partitions.

Innovation Solution

The method involves labeling cells with nucleic acid barcode molecules, either lipophilic or amphiphilic, to enable parallel processing and identification of cells within partitions by sequencing the barcoded nucleic acid molecules, allowing for the determination of cellular occupancy and relative sizes based on barcode uptake.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cells are partitioned into separate partitions for separate processing, then single-cell analysis can be performed in a high-throughput manner, but the ability to process multiple samples in parallel is limited

Engineering Contradiction:
Improvethroughput of single-cell analysisVSAvoidability to process multiple samples in parallel
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The invention segments the identification process by assigning unique barcode sequences to different samples and partitions. Each sample receives a distinct barcode, and each partition receives a distinct barcode, enabling parallel processing of multiple samples while maintaining the ability to track individual cells and partitions through sequencing

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces barcode sequences as intermediary identifiers that mediate between samples, partitions, and cells. These barcodes serve as information carriers that link biological entities to their organizational context, enabling parallel sample processing while maintaining traceability through sequencing-based identification

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If barcode molecules are used to label cells for identification, then cells can be tracked within partitions, but the complexity of the labeling and identification process increases

Engineering Contradiction:
Improveaccuracy of cell identificationVSAvoidcomplexity of barcode labeling and sequencing process
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention uses universal barcode sequences that can identify multiple levels of organization (sample identity, partition identity, and cell identity) through a single labeling approach. The same barcode technology serves multiple functions: sample barcoding, partition barcoding, and cell tracking, reducing the need for separate identification systems

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

Solution Approach 2:

The invention uses nucleic acid barcode sequences that can be copied and amplified through PCR and other molecular biology techniques. This allows a single barcode label on a cell to generate multiple detectable copies during processing, enabling accurate identification without requiring complex detection equipment

Inventive Principle:
Principle #26Copying

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 high-throughput analysis of multiple biological samples by accurately identifying and tracking cells within partitions, facilitating efficient sequencing and analysis of nucleic acid molecules.

Implementation Method 1

barcodes (e.g., nucleic acid barcode sequences) coupled to lipophilic or amphiphilic moieties

Methodology Applied
Scientific EffectPassive diffusion: Diffusion

Data Source

PatentUS20250283180A1Methods and compositions for labeling cells
Publication Date: 2025.09.11 10X GENOMICS INC
  • US20250283180A1 patent drawing
  • US20250283180A1 patent drawing
  • US20250283180A1 patent drawing

AI summary

The present disclosure provides methods, systems, and compositions for parallel processing of nucleic acid samples. Methods and systems of the present disclosure comprise the use of sample-specific barcode sequences, which facilitate the multiplexing of samples, detection of discrete cell populations within a pooled population, and detection of partitions comprising more than one cell.