Microfluidic Cell Segmentation for Precise Single-Cell Analysis

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Solution Overview

Problem

Current methods for analyzing individual cells and defined combinations of cells are limited in their ability to efficiently capture, characterize, and transport cells in a microfluidic system, particularly in terms of scalability and precision in cell selection and manipulation.

Innovation Solution

A method involving multiple rounds of cell capturing, characterization, and transport in a microfluidic system, where cells are flowed into a channel, partitioned into segments, and characterized before being independently transported to specific chambers based on determined characteristics, using a compound manifold system for efficient cell handling and manipulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multiple rounds of cell capturing and transport are performed to achieve precise cell selection and combination, then cell analysis precision is improved, but device complexity and operation time increase

Engineering Contradiction:
Improvecell selection precisionVSAvoidmicrofluidic system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The microfluidic channel is divided into multiple discrete segments that can be independently controlled and manipulated. Each segment can hold individual cells or groups of cells, allowing for precise selection and combination of cells through controlled merging of segments. This segmentation enables complex cell selection protocols without requiring equally complex external control systems.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Cells are pre-positioned and captured in specific segments before the actual analysis or combination step. This preliminary positioning allows for efficient subsequent operations where pre-selected cells can be rapidly combined or analyzed without requiring complex real-time manipulation during the critical analysis phase.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If multiple rounds of cell capturing are performed to handle rare cells effectively, then cell analysis completeness is improved, but processing time increases

Engineering Contradiction:
Improverare cell recoveryVSAvoidprocessing time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The system maintains continuous cell flow and processing through the microfluidic channel, with multiple capturing rounds occurring in parallel or sequence without stopping the overall process. Cells that miss one capture opportunity continue flowing and can be captured in subsequent rounds, ensuring rare cells are not lost while maintaining efficient throughput.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The cell capturing process employs periodic activation of capture mechanisms at different locations along the channel. This periodic action allows the system to systematically process different cell populations or retry captures at optimized intervals, improving rare cell recovery without requiring continuous high-intensity processing that would increase overall time.

Inventive Principle:
Principle #19Periodic action

Data Source

PatentUS10578633B2Methods and devices for analysis of defined multicellular combinations
Publication Date: 2020.03.03 STANDARD BIOTOOLS INC
  • US10578633B2 patent drawing
  • US10578633B2 patent drawing
  • US10578633B2 patent drawing

AI summary

Methods for cell analysis are provided, comprising cell capturing, characterization, transport, and culture. In an exemplary method individual cells (and/or cellular units) are flowed into a microfluidic channel, the channel is partitioned into a plurality of contiguous segments, capturing at least one cell in at least one segment, A characteristic of one or more captured cells is determined and the cell(s) and combinations of cells are transported to specified cell holding chamber(s) based on the determined characteristic(s). Also provided are devices and systems for cell analysis.