Microfluidic Fine Particle Sorting for Single-Cell Emulsion Generation

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Solution Overview

Problem

Current methods for forming emulsions with single cells are inefficient, resulting in a high ratio of empty emulsion particles, which hampers single cell analysis, particularly when dealing with small cell samples like circulating tumor cells.

Innovation Solution

A method involving a fine particle sorting mechanism with a channel structure that includes a main channel, a collection channel, and a liquid supply channel, where a first liquid containing fine particles flows through the main channel, and particles are determined and collected into a second immiscible liquid in the collection channel, forming emulsion particles with a high probability of containing one cell each.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If cells are diluted to achieve one cell per emulsion particle, then empty emulsion particles are reduced, but the efficiency of generating single-cell emulsion particles decreases due to Poisson distribution

Engineering Contradiction:
Improveratio of emulsion particles containing one cellVSAvoidefficiency of generating single-cell emulsion particles
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent applies preliminary action by pre-sorting cells based on their characteristics (size, fluorescence, scattering properties) before emulsion generation. The cell sorting mechanism identifies and selects target cells in advance, ensuring that only desired cells are captured in emulsion particles, thereby eliminating the need for dilution and avoiding empty particles caused by Poisson distribution.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces the mechanical dilution approach with an optical/electrical sorting system. Instead of physically diluting the cell suspension to achieve single-cell distribution, the system uses light scattering, fluorescence detection, and electrical properties to identify and sort individual target cells, which are then captured in emulsion particles with high precision.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If additional cell sorting steps and devices are used to increase single-cell emulsion ratio, then the ratio of emulsion particles containing one cell improves, but the device complexity and process steps increase

Engineering Contradiction:
Improveratio of emulsion particles containing one cellVSAvoidnumber of sorting steps and devices
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent merges the cell sorting function and emulsion generation function into a single integrated device and process. The sorting mechanism, detection system, and emulsion particle formation occur in one continuous flow system, eliminating the need for separate sorting steps and additional devices. This integration maintains high single-cell emulsion ratio while simplifying the overall process.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent implements multi-functionality by designing a system that performs multiple functions simultaneously: cell detection, cell sorting, and emulsion particle generation. The same device components used for detecting cell characteristics are also used to guide the capture process, making the system versatile and eliminating the need for dedicated sorting equipment separate from the emulsion generator.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Quantity of substance

If high-density suspended substances are used to increase single-cell emulsion ratio, then the ratio of emulsion particles containing one cell improves, but the self-organization control becomes complex

Engineering Contradiction:
Improveratio of emulsion particles containing one cellVSAvoidcontrol of self-organization in microchannel
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical control of self-organization with optical and electrical detection methods. Instead of relying on high-density suspensions and complex microchannel flow dynamics to achieve single-cell distribution, the system uses light scattering, fluorescence, and electrical property detection to identify and sort individual cells, which are then captured in emulsion particles through controlled flow mechanisms.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 method significantly increases the ratio of emulsion particles containing one cell, enhancing the efficiency of single cell analysis by reducing the need for additional cell sorting steps and devices, and allowing for high-throughput analysis even with limited cell samples.

Implementation Method 1

a flow step of causing a first liquid containing the fine particles to flow through the main channel

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Implementation Method 2

an emulsion containing the second liquid as a dispersion medium and the first liquid as a dispersoid can be formed in the collection channel

Methodology Applied
Scientific EffectEmulsion formation: Emulsion

Data Source

PatentUS20220396757A1Method of collecting fine particles, microchip for sorting fine particles, device for collecting fine particles, method of producing emulsion, and emulsion
Publication Date: 2022.12.15 SONY GROUP CORP
  • US20220396757A1 patent drawing
  • US20220396757A1 patent drawing
  • US20220396757A1 patent drawing

AI summary

Provided is a new method for more efficiently generating emulsion particles each containing one fine particle.The present technology provides a method of collecting fine particles, in which in a fine particle sorting mechanism having a channel structure including a main channel through which the fine particles flow, a collection channel into which particles to be collected are collected from among the fine particles, a connection channel that connects the main channel and the collection channel, and a liquid supply channel connected to the connection channel so as to supply a liquid, the method includes: a flow step of causing a first liquid containing the fine particles to flow through the main channel; a determination step of determining whether or not the fine particles flowing through the main channel are the particles to be collected; and a collection step of collecting the particles to be collected into the collection channel, and, in the collection step, the particles to be collected are collected into a second liquid that is immiscible with the first liquid in the collection channel while being contained in the first liquid.