Sequence-Tagged Antibody Conjugate for Single Cell Analysis
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Solution Overview
Problem
Current methods lack a reagent and approach to combine various modalities for cell enrichment, sorting, and genomic analysis, leading to high costs and inefficiencies due to the need for multiple reagents and sequential workflows, particularly in single-cell sequencing and imaging applications.
Innovation Solution
A sequence-tagged fluorescent-label specificity determining molecule conjugate is used for cell enrichment, sorting, and immunofluorescent labeling, which can also be employed in genomic analysis, enabling a single reagent to perform multiple functions and integrate different measurement modalities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple reagents are used for cell enrichment, sorting, and genomic analysis, then each function can be performed with dedicated optimization, but the cost and complexity increase significantly
Solution Approach 1:
The patent applies universality by designing a single reagent that performs multiple functions: cell enrichment, sorting, and genomic analysis. This reagent contains both a binding component for cell surface markers and a barcode component for genomic identification, eliminating the need for separate reagents for each function and thereby reducing complexity while maintaining functional optimization.
Solution Approach 2:
The patent merges previously separate functions into a single reagent system. The binding component and barcode component are combined in one reagent molecule, allowing simultaneous cell enrichment and genomic analysis in a single experiment, thus reducing the number of reagents and simplifying the workflow.
2Reliability
If multiple reagents are used for cell enrichment and genomic analysis, then each step can be optimized independently, but the overall cost increases
Solution Approach 1:
The patent reduces reagent cost by designing a universal reagent that performs multiple functions including cell enrichment and genomic analysis. This eliminates the need to purchase and use separate reagents for each function, thereby reducing the total quantity of reagents consumed and the overall cost while maintaining functional optimization through careful design of the binding and barcode components.
3Reliability
If sequential workflows are used for cell sorting and genomic analysis, then each step can be performed with dedicated reagents, but the time required and efficiency decrease
Solution Approach 1:
The patent combines cell sorting and genomic analysis into a single simultaneous experiment using a unified reagent system. The binding component enables cell sorting while the barcode component enables genomic analysis, both performed in parallel rather than sequentially, thereby reducing workflow time and improving efficiency while maintaining functional optimization.
Solution Approach 2:
The universal reagent enables multiple functions to be performed simultaneously in a single experiment, eliminating the need for sequential workflows. This multi-functional approach reduces the total time required while maintaining the functional optimization that would be achieved through dedicated reagents for each function.
4Reliability
If different reagents are used for imaging and genomic analysis, then each modality can be optimized, but the ability to integrate measurements is lost
Solution Approach 1:
The patent creates a universal reagent that enables both imaging and genomic analysis functions. The binding component allows for imaging applications while the barcode component enables genomic analysis, thereby integrating multiple measurement modalities into a single experiment while maintaining the optimization benefits of dedicated reagents for each function.
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 reduces costs and enhances efficiency by allowing simultaneous cell enrichment, sorting, and genomic analysis, improving the ability to measure both protein and RNA in a single experiment with improved sensitivity and reduced sequencing depth requirements.
Implementation Method 1
a fluorescent label component and a specificity determining molecule component, wherein one or more components of the conjugate are used for cell enrichment, cell sorting, and/or immunofluorescent cell labeling
Implementation Method 2
the nucleic acid linker comprises a double-stranded segment
Data Source
AI summary
Provided herein are multimodal methods and compositions that combine sequence-tagged antibodies and fluorescent labels in a single reagent. Combined with optimal panel design, high-purity sorting of cells before sequencing has been demonstrated, and furthermore, truly quantitative information on the cell surface markers used for sorting.