Vibrating Cell Sorter Resolves Purity and Survival Trade-off

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Solution Overview

Problem

Current cell sorting techniques, such as flow cytometry and magnetic activated cell sorting, are limited by the requirement for specific surface markers on cells, which are not always present, especially in cancer cells, and alternative methods like dielectrophoresis do not ensure cell survival or provide sufficient resolution.

Innovation Solution

A device with a vibrating support, using a suspended membrane and piezoelectric actuators, applies inertial forces to detach cells based on their adhesion properties, allowing for selective sorting without prior marking, by vibrating the support at specific frequencies to detach cells of interest while keeping others adhered.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If flow cytometry or magnetic activated cell sorting is used, then cell sorting purity is improved, but device complexity and cost increase

Engineering Contradiction:
Improvecell sorting purityVSAvoidequipment complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies mechanical vibration to a substrate at specific frequencies to detach cells based on their adhesion properties. By vibrating the substrate at resonant frequencies, cells with weaker adhesion forces are selectively detached, enabling sorting without complex optical or magnetic systems. This resolves the contradiction by achieving effective cell separation through simple mechanical means rather than expensive flow cytometry or magnetic sorting equipment.

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The patent changes the physical parameter of vibration frequency to control cell detachment. By adjusting the frequency and amplitude of substrate vibration, different cell populations with varying adhesion strengths can be selectively detached. This parameter-based control enables simple, cost-effective cell sorting that achieves high purity without requiring complex devices or specific cell surface markers.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If dielectrophoresis is used for cell sorting, then sorting without prior marking is achieved, but cell survival deteriorates

Engineering Contradiction:
Improvesorting without markingVSAvoidcell survival
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent replaces the harsh electrical fields of dielectrophoresis with gentle mechanical vibration. The vibrational forces selectively detach cells based on adhesion properties without exposing cells to high-voltage electrical fields that can damage cell membranes. This achieves marker-free sorting while preserving cell viability, resolving the contradiction between sorting versatility and cell survival.

Inventive Principle:
Principle #18Mechanical vibration

3Productivity

If shear stress is applied to detach adhered cells, then cell recovery is improved, but uniformity of detachment deteriorates

Engineering Contradiction:
Improvecell recovery efficiencyVSAvoiddetachment uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent uses mechanical vibration of the substrate instead of fluid shear stress to detach cells. Vibration provides uniform forces across the entire substrate surface, ensuring consistent detachment conditions for all adhered cells. By tuning the vibration frequency and amplitude, complete and uniform detachment of target cell populations is achieved, resolving the contradiction between recovery efficiency and detachment uniformity.

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The patent applies periodic vibrational motion to the substrate to detach cells. The oscillating forces create repeated stress cycles that uniformly overcome adhesion bonds across the substrate surface. This periodic action ensures consistent detachment of cells with adhesion strengths below the vibration threshold, achieving both high recovery efficiency and uniform detachment across the entire cell population.

Inventive Principle:
Principle #19Periodic 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

This method enables efficient and discriminatory manipulation of biological cells, particularly cancer cells, by modifying adhesion forces through vibration frequency, ensuring high purity and cell survival during the sorting process.

Implementation Method 1

piezoelectric actuators

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

applies inertial forces to detach cells based on their adhesion properties

Methodology Applied
Scientific EffectInertial force: Inertia

Data Source

PatentEP3059300B1Device for manipulating biological cells using a vibrating holder
Publication Date: 2021.08.11 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP3059300B1 patent drawingFigure 1~3
  • EP3059300B1 patent drawingFigure 4
  • EP3059300B1 patent drawingFigure 5~6B

AI summary

A device for sorting living cells, comprising at least one support (12) including a surface having adhesion properties with respect to said type of living cells, actuators (14, 16) capable of vibrating said surface at at least one given frequency and means for controlling the actuators (14, 16) so that the surface vibrates at a frequency causing the detachment of at least one type of living cells.