Cell Labeling Molecule for Non-Destructive Nucleic Acid Association
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Solution Overview
Problem
Existing cell labeling methods fail to associate non-destructive information with nucleic acid sequences, especially when multiple cells are present in a compartment, leading to mixed nucleic acids and difficulty in distinguishing individual cell information, particularly for adherent cells or cells within tissues.
Innovation Solution
A cell labeling molecule comprising a particle with an identifiable property, an identification sequence, a cleavable linker, and a binding molecule that can bind to cells, allowing for the association of non-destructive information with nucleic acid sequences through optical detection and isolation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a cell is lysed in a compartment to extract nucleic acid, then the nucleic acid can be obtained for analysis, but the non-destructive information of the cell is lost and cannot be associated with the nucleic acid sequence
Solution Approach 1:
The invention divides the cell processing into separate compartments: one compartment for non-destructive imaging to capture non-destructive information, and another compartment for lysis to extract nucleic acid. The cell is physically segmented between these two functional zones, allowing both information types to be obtained without interference.
Solution Approach 2:
The non-destructive imaging is performed before the cell is lysed. By capturing the non-destructive information in advance, the system ensures that this information is preserved and can be subsequently associated with the nucleic acid sequence obtained after lysis, rather than losing it during the extraction process.
2Productivity
If more than one cell is placed in a compartment for analysis, then the throughput is improved, but the nucleic acids of multiple cells mix up and individual cell information cannot be distinguished
Solution Approach 1:
The invention uses multiple separate compartments instead of a single compartment to hold multiple cells. Each compartment contains at most one cell, preventing nucleic acid mixing. The compartmentalization strategy segments the sample population into individual processing units, maintaining both high throughput and individual cell resolution.
Solution Approach 2:
The invention uses beads with identification sequences that serve as proxies or copies for identifying individual cells. Each bead is associated with a specific cell through co-localization in a compartment, and the bead's identification sequence allows tracking and association of that cell's non-destructive information with its nucleic acid sequence, even after the cell is lysed.
3Adaptability or versatility
If adherent cells or cells within tissues are analyzed, then clinically relevant samples can be studied, but it is difficult to place them in compartments for standard analysis
Solution Approach 1:
The invention changes the physical state or form of the sample by using tissue dissociation reagents to convert tissue samples into suspensions of individual cells. This parameter change (from intact tissue to cell suspension) enables the cells to be properly distributed into compartments for analysis, while still preserving the ability to study clinically relevant samples.
Data Source
AI summary
A cell labeling molecule comprising a particle 101 having an identifiable property, an identification sequence 102 that is identifiable and corresponds to the property of the particle 101, a cleavable linker 103 that binds the particle 101 and the identification sequence 102, and a binding molecule 104 for binding to a cell, the binding molecule being bound to the identification sequence 102.