Barcoded MHC Droplet System for Single-Cell Multi-Analyte Detection
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Solution Overview
Problem
Current methods lack efficient techniques for analyzing multiple analytes, such as genomic, epigenomic, and proteomic information, from individual cells or small populations, particularly for cells like cancer cells, fetal cells, and immune cells, which are crucial for disease detection and characterization.
Innovation Solution
A method involving the use of droplets or wells containing MHC molecules, peptide molecules, and nucleic acid molecules with barcode sequences, where these molecules are attached and recovered to identify specific cells, including T-cells, through sequencing of barcoded nucleic acid molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used for analyzing multiple analytes from individual cells, then the analysis can be performed, but the efficiency and accuracy are insufficient for detecting rare cells like cancer cells, fetal cells, and immune cells
Solution Approach 1:
The method partitions a population of cells into individual partitions (droplets or wells), allowing each cell to be analyzed separately. This segmentation enables the detection of rare cells among millions by isolating them in individual compartments, where they can be identified and characterized without being lost in the bulk population.
Solution Approach 2:
The invention implements a nested barcoding system where multiple levels of barcodes are combined: a first barcode identifies the partition, a second barcode identifies the cell within the partition, and additional barcodes identify specific analytes. This nested structure allows comprehensive tracking and identification of rare cells through multiple hierarchical levels.
2Adaptability or versatility
If multiple analytes are analyzed from individual cells using current methods, then comprehensive information can be obtained, but the process becomes complex and time-consuming
Solution Approach 1:
The method employs universal barcoding reagents and protocols that can simultaneously analyze multiple types of analytes (genomic, epigenomic, transcriptome, and proteomic information) from the same cell. The same partitioning and barcoding system works for different analyte types, reducing the need for separate complex procedures for each analyte class.
Solution Approach 2:
The invention performs preliminary barcoding of cells and partitions before analyzing different analyte types. By establishing the barcode identification system in advance, subsequent analyses of genomic, epigenomic, transcriptome, or proteomic information can be performed on the same pre-barcoded cells, streamlining the overall process and reducing complexity.
3Measurement precision
If barcoded nucleic acid molecules are sequenced to identify specific cells, then accurate cell attribution is achieved, but the sequencing cost and time increase
Solution Approach 1:
The method extracts and amplifies only the specific barcode sequences from the barcoded nucleic acid molecules rather than sequencing entire genomes. By isolating and sequencing only the relevant barcode regions that identify cells and partitions, the sequencing time and cost are dramatically reduced while maintaining accurate cell identification capability.
Data Source
AI summary
The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing and analyte characterization from a single cell. Such polynucleotide processing may be useful for a variety of applications. The compositions, methods, systems, and devices disclosed herein generally describe barcoded oligonucleotides, which can be bound to a bead, such as a gel bead, useful for characterizing one or more analytes including, for example, protein (e.g., cell surface or intracellular proteins) and chromatin (e.g., accessible chromatin).