Single-Cell Analyte Processing With Origin-Tracking Barcodes
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Solution Overview
Problem
Existing methods struggle to accurately and efficiently identify the origin of analytes, such as proteins and metabolites, at the single cell level during sample processing.
Innovation Solution
A method involving the use of cell beads and nucleic acid barcode molecules to couple with specific or non-specific antibodies, allowing for the generation of composite barcode sequences that can be sequenced to determine the origin of analytes within a cell.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional sample processing methods are used, then processing can be performed, but the origin of analytes cannot be accurately identified at the single cell level
Solution Approach 1:
The patent introduces nucleic acid barcode molecules as intermediary carriers that bridge the connection between cells and analytes. These barcode molecules are incorporated into analytes during processing and serve as traceable identifiers that preserve cell origin information throughout the analytical process, enabling accurate tracking of analyte origins without direct cell-analyte physical connection
Solution Approach 2:
The patent creates informational copies of cell identity through nucleic acid barcode sequences. Instead of directly analyzing cells, the system generates barcode copies that encode cell origin information and attaches them to analytes, allowing indirect but accurate identification of analyte origins through sequencing these barcode copies
2Measurement precision
If single cell level analysis is performed, then analyte origin can be identified, but processing complexity increases
Solution Approach 1:
The patent employs universal nucleic acid barcode molecules that can be applied across different cell types and analyte classes. The same barcode incorporation mechanism and sequencing approach works for various proteins, metabolites, and cell types, reducing the need for specialized complex procedures for each specific analysis scenario
Solution Approach 2:
The patent replaces complex mechanical single-cell isolation and tracking systems with a biochemical information encoding system. Instead of physically tracking individual cells through complex mechanical means, the system uses nucleic acid barcode molecules to encode and transmit cell origin information, simplifying the overall processing architecture
3Quantity of substance
If antibodies are used to capture analytes, then specific analytes can be isolated, but the connection to original cell is lost
Solution Approach 1:
The patent merges the analyte capture function of antibodies with the information encoding function of nucleic acid barcodes into a unified system. The barcode molecules are incorporated into the antibody-analyte complex during the capture process itself, combining the benefits of specific analyte isolation with automatic origin tracking without requiring separate steps
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 accurate and efficient identification of analytes at the single cell level by attributing them to their originating cells through nucleic acid sequencing, facilitating precise measurement and analysis.
Implementation Method 1
bringing a cell bead generated from the cell in contact with an antibody having binding specificity with the protein, under conditions sufficient to permit the antibody to flow into the cell bead and couple to the protein
Implementation Method 2
sequencing the nucleic acid molecule or derivative thereof to identify the first nucleic acid sequence and the second nucleic acid sequence
Data Source
AI summary
The present disclosure provides systems and methods for measuring one or more analytes at the single cell level. In some instances, sequencing of a composite barcode sequence may identify a type of analyte, identify a cell, and determine that the type of analyte originated from the cell. In some instances, a probability that a type of analyte originated from the cell may be determined. Multiple types of analytes may be identified to have originated from the cell, and/or the respective probabilities determined. An analyte may be a protein, such as a surface-bound protein or an internal protein. An analyte may be a metabolite or other small molecule. An analyte may be any constituent of a cell.