Particle Purification by Repeated Sorting for High-Concentration Samples

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Solution Overview

Problem

Conventional cell sorting and dispensing technologies face challenges such as high cell damage, low throughput, contamination, limited droplet size, and difficulty in handling water in oil droplets, especially in fluorocarbon oil, and inadequate analysis of cell clusters.

Innovation Solution

A method and apparatus for purifying target particles by repeated sorting, dispensing single particles using a flow-path chip with controlled air pressure, and analyzing cell clusters based on scattered light signal ratios.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional Jet in Air type cell sorter is used to separate cells into individual droplets, then sorting speed is improved, but cell damage increases due to high-speed collision with collection tube wall

Engineering Contradiction:

Improvesorting speedVSAvoidcell damage

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a collection reservoir filled with sheath liquid as an intermediary medium between the droplet ejection system and the final collection container. The droplets are deposited into the sheath liquid rather than directly colliding with the collection tube wall, significantly reducing mechanical impact and cell damage while maintaining high sorting throughput

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If conventional micro flow path sorting is used, then cell damage is reduced, but sorting throughput decreases to about 1000 cells per second or less

Engineering Contradiction:

Improvecell damageVSAvoidsorting throughput

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent divides the sorting process into two distinct stages: (1) high-speed droplet generation and initial separation using Jet in Air technology, and (2) gentle deposition and collection in a reservoir with sheath liquid. This segmentation allows each stage to optimize for its specific function, achieving both high throughput and low cell damage

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The sheath liquid in the collection reservoir serves as a protective intermediary that cushions the deposited droplets, preventing direct impact with the collection container walls while maintaining the benefits of high-speed initial separation

Inventive Principle:

Principle #24Intermediary (Mediator)

3Manufacturing precision

If repeated sorting is performed to purify target particles from high concentration samples, then purification purity is improved, but processing time increases

Engineering Contradiction:

Improvepurification purityVSAvoidprocessing time

Core Design Contradiction:

Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary concentration of target particles into a small volume within the collection reservoir before the repeated sorting process. This preliminary action reduces the initial particle concentration that needs to be processed, thereby significantly reducing the total processing time required for achieving high purification purity through subsequent repeated sortings

Inventive Principle:

Principle #10Preliminary action

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

Enables rapid purification of target particles from high-concentration samples, reliable dispensing of single particles and water in oil droplets, and accurate determination of cell clusters, reducing processing time and improving purity.

Implementation Method 1

a ratio between a forward scattered light signal intensity and a scattered light signal intensity other than forward detected in each cell is calculated, and by the obtained value of the ratio, whether individual cells are single cells or cell cluster are identified

Methodology Applied

Scientific EffectLight scattering: Scattering

Implementation Method 2

a liquid flow in the flow paths is controlled by an air pressure above each reservoir

Methodology Applied

Scientific EffectPressure-driven flow: Pressure Gradient

Implementation Method 3

a pulse flow is generated for a short time, and the target particles are taken into the collection reservoir (2) through the collection flow path (10)

Methodology Applied

Scientific EffectPulsed flow separation:

Data Source

PatentUS12453969B2Method for purifying particles, method for dispensing a single particle, method for analyzing cell cluster, and apparatus using the same

Publication Date: 2025.10.28 ON CHIP BIOTECH

AI summary

One object of the present invention is to provide a method or apparatus for purifying target particles from high-concentration particles in a short time. The above problem can be solved by a method for purifying target particles, characterized in that the method comprises a step of sorting the target particles from a high concentration of non-target particles, wherein the sorting step is repeated for three times or more.