Single-Cell Sample Indexing for Joint Protein and Gene Analysis

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current technologies are limited in their ability to quantitatively analyze protein expression and protein-protein interactions in cells, while also measuring gene expression in a massively parallel manner.

Innovation Solution

A method involving sample indexing compositions with antigen binding reagents conjugated to sample indexing oligonucleotides, allowing for barcoding and sequencing to identify the origin of cells based on unique sequences, enabling simultaneous measurement of protein and gene expression and protein-protein interactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If current technology is used to measure gene expression in a massively parallel manner, then gene expression measurement capability is improved, but the ability to quantitatively analyze protein expression and protein-protein interactions deteriorates

Engineering Contradiction:

Improvenumber of cells measuredVSAvoidprotein expression analysis capability

Core Design Contradiction:

Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent combines gene expression measurement and protein expression measurement into a single massively parallel sequencing platform. By integrating both measurement capabilities in one system, the patent enables simultaneous quantitative analysis of both gene and protein expression across thousands of cells, resolving the contradiction between high-throughput capability and protein analysis precision

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent creates a universal measurement platform that performs multiple functions: measuring gene expression, measuring protein expression, and analyzing protein-protein interactions. This multi-functional approach allows the system to handle diverse measurement needs within a single framework, improving both throughput and measurement precision across different molecular targets

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If sample indexing compositions with multiple antigen binding reagents are used, then the ability to identify sample origin and analyze protein expression is improved, but the complexity of the system increases

Engineering Contradiction:

Improvesample origin identification accuracyVSAvoidsystem complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the identification system into distinct modular components: sample indexing compositions with unique barcodes, antigen binding reagents with specific targets, and sequencing readout. This segmentation allows each component to be optimized independently while maintaining overall system functionality, managing complexity through modularity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces sample indexing oligonucleotides as intermediary molecules that bridge the antigen binding reagents and the sequencing detection system. These intermediaries carry unique sample identifiers that enable traceability without requiring direct complex interactions between all system components, simplifying the overall architecture

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If molecular barcoding is implemented to identify cell origin, then data interpretation efficiency is improved, but the complexity of sample processing increases

Engineering Contradiction:

Improvedata interpretation efficiencyVSAvoidsample processing complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent uses molecular barcodes as information copies that are attached to cellular components. These barcodes serve as simplified representations of complex cellular identities, enabling efficient data interpretation through sequence reading without requiring direct analysis of the entire cellular proteome or transcriptome

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent performs barcoding of samples before the main measurement process. By pre-attaching unique molecular identifiers to cells or cellular components at an early stage, the system establishes a tracking framework that simplifies subsequent data interpretation and analysis steps

Inventive Principle:

Principle #10Preliminary action

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 the quantitative analysis of protein expression and protein-protein interactions, while identifying the origin of cells through molecular barcoding, facilitating efficient data interpretation.

Implementation Method 1

at least one of the two or more antigen binding reagents is capable of specifically binding to at least one of the one or more antigen targets

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS12371729B2Sample indexing for single cells

Publication Date: 2025.07.29 BECTON DICKINSON & CO

AI summary

Disclosed herein include systems, methods, compositions, and kits for sample identification. A sample indexing composition can comprise, for example, a protein binding reagent associated with a sample indexing oligonucleotide. Different sample indexing compositions can include sample indexing oligonucleotides with different sequences. Sample origin of cells can be identified based on the sequences of the sample indexing oligonucleotides. Sample indexing oligonucleotides can be barcoded using barcoded and lengthened using daisy-chaining primers.