Single-Cell Well Partitioning to Prevent Target Material Leakage
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Solution Overview
Problem
Existing cell capture and processing systems face issues with leakage and non-specific capture of biological target materials, such as mRNA and proteins, between chambers or partitions, which compromises the integrity of downstream assays.
Innovation Solution
A system and method for single cell capture and processing that includes a substrate with an array of wells, a fluid delivery module, thermal control, and imaging subsystem, designed to isolate and analyze cells at known locations, prevent leakage, and facilitate controlled biochemical reactions, including real-time cell tracking and molecular analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If cells are captured in an array of wells for single-cell analysis, then cell isolation and identification capability is improved, but leakage of target material between chambers occurs
Solution Approach 1:
A partitioning fluid is introduced as an intermediary substance between adjacent wells to prevent target material leakage. The partitioning fluid forms a barrier that isolates target material within each well while allowing the wells to remain in close proximity for high-density array configuration.
Solution Approach 2:
The system segments the continuous space into discrete, isolated compartments (wells) using partitioning fluid. This segmentation allows each well to function as an independent reaction chamber while maintaining overall system integration for high-throughput processing.
2Productivity
If wells are placed in close proximity for high-density arrays, then throughput and analysis efficiency is improved, but target material drifts between adjacent chambers
Solution Approach 1:
The partitioning fluid acts as a mediator that enables close well spacing without target material cross-contamination. It fills the inter-well space and prevents target material drift while allowing the high-density array configuration needed for high throughput.
Solution Approach 2:
The system changes the physical state or properties of the partitioning fluid to optimize its barrier function. By controlling parameters such as fluid density, viscosity, or surface tension, the partitioning fluid effectively prevents target material leakage while maintaining system productivity.
3Reliability
If partitioning fluid is introduced to prevent leakage, then target material containment is improved, but system complexity and processing steps increase
Solution Approach 1:
The partitioning fluid serves multiple functions simultaneously: it prevents target material leakage between wells, maintains well isolation during processing, and enables high-density array configuration. This multi-functionality reduces the need for additional complex containment structures.
Solution Approach 2:
The partitioning fluid self-organizes to form barriers between wells through capillary action or surface tension, eliminating the need for complex mechanical partition structures. The fluid automatically positions itself to prevent leakage without requiring additional actuation mechanisms.
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
The system effectively captures and processes cells in single-cell format, preventing leakage and non-specific capture, enabling efficient downstream assays and genetic library preparation, while maintaining cell viability and facilitating high-throughput analysis.
Implementation Method 1
retaining intercellular material of the set of target cells, individually with the set of particles within the array of wells, with transmission of heat into the array of wells
Implementation Method 2
preventing evaporation of contents of the array of wells upon receiving a partitioning fluid into the cavity
Implementation Method 3
partitioning each of the array of wells from adjacent wells of the array of wells, at the surface plane, upon displacing the lysis buffer from the cavity with a gas volume
Data Source
Figure 1A~1B
Figure 2A~2C
Figure 3
AI summary
A system and method for target material capture, the method comprising: receiving a set of target cells into an array of wells defined at a surface plane of a substrate; receiving a set of particles into the array of wells, thereby co-capturing the set of target cells and the set of particles; achieving a desired state for the array of wells upon receiving a washing fluid into a cavity in communication with the array of wells; receiving a lysis buffer into the cavity; receiving a partitioning fluid into the cavity, thereby displacing the lysis buffer from the cavity and partitioning each of the array of wells from adjacent wells, at the surface plane; and retaining intracellular material of the set of target cells, individually with the set of particles within the array of wells.