Acoustic Cell Separation Reducing Aggregation and Damage

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Solution Overview

Problem

Current methods for processing biological samples, such as flow cytometry, face challenges with cell washing and concentration, as they can be time-consuming and may damage cells or lead to aggregation, and require laborious protocols for disaggregation, which can be inefficient and detrimental to cell viability.

Innovation Solution

A method and system that acoustically separates cells from cellular debris and non-cellular macromolecules, using acoustic and magnetic separation techniques to break up cell aggregates and separate individual cells, reducing cell damage and improving processing efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If manual centrifugation is used for cell washing and concentration, then cell processing is achieved, but processing time increases and cell damage occurs

Engineering Contradiction:
Improveprocessing speedVSAvoidcell damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces manual centrifugation with an automated acoustic separation system that uses acoustic waves to separate cells from biological material. This substitution eliminates the mechanical stress and time-consuming manual operations of centrifugation while achieving effective cell isolation and concentration.

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

Solution Approach 2:

The patent introduces acoustic waves as an intermediary force to separate cells from biological material. The acoustic field acts as a mediator that enables separation without direct mechanical contact or centrifugal forces, thereby reducing cell damage while maintaining processing efficiency.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If extended periods of mechanical disaggregation or enzymatic treatment are applied, then cell aggregates are broken up, but cell viability decreases due to over-processing

Engineering Contradiction:
Improvedisaggregation completenessVSAvoidcell viability
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent replaces prolonged mechanical disaggregation and enzymatic treatment with acoustic separation technology. This substitution achieves complete disaggregation of cell aggregates without the need for extended processing times, thereby preserving cell viability while maintaining disaggregation effectiveness.

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

Solution Approach 2:

The patent employs periodic acoustic waves to disaggregate cell aggregates. This periodic action effectively breaks up aggregates without requiring continuous prolonged treatment, thus avoiding over-processing damage and maintaining high cell viability while achieving complete disaggregation.

Inventive Principle:
Principle #19Periodic action

3Productivity

If cells are washed and concentrated using traditional methods, then cell preparation is achieved, but cell aggregation increases

Engineering Contradiction:
Improvecell concentration efficiencyVSAvoidcell aggregation
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent replaces traditional washing and concentration methods with acoustic separation technology. This substitution effectively concentrates cells while preventing aggregation through the gentle action of acoustic forces, maintaining both processing efficiency and cell dispersion stability.

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

Solution Approach 2:

The patent utilizes acoustic field parameters to control cell separation and concentration. By adjusting acoustic frequency and intensity parameters, the system achieves effective cell concentration while maintaining cells in a dispersed state, preventing aggregation during the concentration process.

Inventive Principle:
Principle #35Parameter changes

4Manufacturing precision

If laborious purification and separation protocols are used, then disaggregated cells are separated from tissue, but processing complexity increases

Engineering Contradiction:
Improveseparation purityVSAvoidprotocol complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent replaces laborious purification and separation protocols with a single acoustic separation step. This substitution achieves high separation purity by effectively separating disaggregated cells from tissue and other biological material, while dramatically simplifying the overall processing protocol and reducing operational complexity.

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

The method effectively reduces cell aggregation, enhances processing efficiency, and improves cell viability by using acoustic and magnetic separation to isolate cells from biological samples, facilitating the production of samples with low entrainment and optimal cell collection.

Implementation Method 1

acoustically separating larger components of the disrupted biological sample from smaller components

Methodology Applied
Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Implementation Method 2

magnetically separating magnetically labelled moieties from unlabeled moieties

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Data Source

PatentEP3087194B1Devices and methods for processing a biological sample
Publication Date: 2021.06.16 BECTON DICKINSON & CO
  • EP3087194B1 patent drawingFigure 1
  • EP3087194B1 patent drawingFigure 2
  • EP3087194B1 patent drawingFigure 3

AI summary

Aspects of the present disclosure include methods for processing a biological sample. Methods according to certain embodiments include disrupting a biological sample to produce a disrupted biological sample and acoustically separating larger components from smaller components in the disrupted biological sample. In certain embodiments, methods may include monitoring aggregation while the biological sample is being processed. Methods, in certain instances, also include acoustically separating cells from cellular debris and non-cellular macromolecules as well as magnetically separating magnetically labelled moieties from unlabeled moieties. Systems, including a disrupter, one or more acoustic concentrator devices, feedback monitors and magnetic separation devices suitable for practicing the subject methods are also described.