Recirculating Fluid Ejection Channels for Label-Free Cell Sorting

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Solution Overview

Problem

Current cell sorting technologies are inefficient and often rely on labeling agents, which can interfere with cellular operations and analysis, and existing label-free methods are either expensive or result in inaccurate sorting due to the presence of non-target cells and clumps.

Innovation Solution

An automated, low-cost single-cell sorting system that uses a recirculating fluid ejection system with sensors and fluid ejectors to selectively sort and dispense target cells based on size and type, separating fluid pumping and ejection operations to ensure precise targeting and minimize waste.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If labeling agents are used for cell sorting, then cell identification accuracy is improved, but cellular operation interference increases

Engineering Contradiction:
Improvecell identification accuracyVSAvoidcellular operation interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes labeling agents from the cell sorting process entirely. Instead of using fluorescent tags or chemical labels that interfere with cellular operations, the system uses label-free detection methods where sensors directly detect cell properties such as size, shape, and electrical characteristics as cells pass through measurement zones in the fluid ejection channels.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces chemical labeling mechanisms with physical detection mechanisms. Electrical sensors and optical detection systems directly measure cell properties without requiring chemical labels, substituting the mechanical/physical detection process for the chemical labeling approach that caused interference with cellular operations.

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

2Object-affected harmful factors

If label-free methods are used, then cellular operation interference is reduced, but sorting accuracy deteriorates due to non-target cells and clumps

Engineering Contradiction:
Improvecellular operation interferenceVSAvoidsorting accuracy
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent segments the fluid ejection system into multiple parallel channels, each with its own sensor array and ejection mechanism. This segmentation allows independent optimization of detection parameters for each channel and enables selective ejection of target cells based on their specific physical characteristics while maintaining high sorting accuracy without label interference.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements dynamic control of fluid ejection based on real-time sensor feedback. The system continuously monitors cell properties as they pass through the channels and dynamically activates or deactivates ejection mechanisms based on whether detected cells match target criteria, enabling high-precision sorting of individual cells while rejecting non-target cells and clumps.

Inventive Principle:
Principle #15Dynamics

3Measurement precision

If existing cell sorting technologies are used, then cell separation is achieved, but system complexity and cost increase

Engineering Contradiction:
Improvecell separation accuracyVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent designs fluid ejection channels that serve multiple functions: they transport cells, house sensor arrays for detection, provide ejection mechanisms for separation, and enable recirculation of non-target cells. This multi-functionality reduces the number of separate components needed compared to traditional sorting systems that require separate channels for each function.

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

Solution Approach 2:

The patent implements a recirculation system where non-target cells and excess fluid are automatically returned to the input reservoir for reprocessing. This recirculation mechanism simplifies the overall system by eliminating the need for separate waste disposal systems and allowing continuous operation with a single input stream, reducing both complexity and operational cost.

Inventive Principle:
Principle #34Discarding and recovering

4Device complexity

If fluid pumping and ejection are combined, then device complexity is reduced, but ejection precision deteriorates

Engineering Contradiction:
Improvedevice complexityVSAvoidejection precision
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The patent segments the fluid handling system into distinct pumping and ejection functions. A separate pump system provides controlled fluid flow through the channels, while independent ejection mechanisms at each channel outlet enable precise, on-demand cell ejection. This segmentation allows optimization of each function independently, achieving high ejection precision without requiring complex integrated designs.

Inventive Principle:
Principle #1Segmentation

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 achieves highly accurate and efficient separation of single cells, reducing the need for labeling agents and minimizing contamination, thereby enhancing the reliability and accuracy of subsequent cellular analyses.

Implementation Method 1

a sensor to detect a presence in the fluid of a target particle to be ejected

Methodology Applied
Scientific EffectElectrical impedance detection: Electrical Resistance

Implementation Method 2

a fluid ejector to eject the target particle from the fluid ejection channel

Methodology Applied
Scientific EffectAcoustic ejection: Acoustic Radiation Pressure

Implementation Method 3

a pump to move fluid through a respective fluid ejection channel

Methodology Applied
Scientific EffectPressure gradient: Pressure Gradient

Data Source

PatentEP4143534B1Target particle ejection from recirculating fluid ejection channels
Publication Date: 2024.09.25 HEWLETT PACKARD DEVELOPMENT COMPANY LP
  • EP4143534B1 patent drawingFigure 1
  • EP4143534B1 patent drawingFigure 2
  • EP4143534B1 patent drawingFigure 3

AI summary

In one example in accordance with the present disclosure, am ejection system is described. The ejection system includes a fluid feed slot to supply fluid to a number of fluid ejection channels where each fluid ejection channel is a recirculating channel. Each fluid ejection channel includes a sensor to detect, in the fluid, a target particle to be ejected and a fluid ejector to eject the target particle from the fluid ejection channel. The ejection system also includes a controller to selectively activate the fluid ejector when the target particle presence is detected. Non-target particles are returned to the fluid feed slot past the fluid ejector.