Acoustophoretic Reflector for Bioreactor Cell Separation

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Solution Overview

Problem

Current bioreactor systems for producing biomolecules like recombinant proteins and monoclonal antibodies face high costs and inefficiencies due to the need for complex cell retention devices and costly filtration processes, which lead to non-productive downtime and material loss.

Innovation Solution

The implementation of an acoustophoretic device that uses multi-dimensional acoustic standing waves generated by ultrasonic transducers and a thin, acoustically transparent reflector to separate cells and cell debris from the desired products, allowing for efficient clustering and gravity separation without the need for traditional filtration methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional filtration methods are used to separate cells and cell debris from biomolecules, then separation can be achieved, but equipment complexity increases and non-productive downtime occurs

Engineering Contradiction:
Improvebioreactor productivityVSAvoidcell retention device complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent replaces mechanical filtration systems with an acoustophoretic separation system that uses acoustic standing waves to separate cells and cell debris from biomolecules. The ultrasonic transducer generates acoustic radiation pressure that selectively traps cells at nodes while allowing biomolecules to pass through, eliminating the need for complex mechanical filters and reducing equipment downtime.

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

Solution Approach 2:

The patent extracts and removes the cell retention function from the traditional filtration system by implementing a disposable flow chamber with integrated acoustophoretic separation. This allows the separation mechanism to be built into the flow chamber itself rather than requiring separate complex retention equipment, thereby simplifying the overall system.

Inventive Principle:
Principle #2Taking out (Extraction)

2Manufacturing precision

If costly filtration processes are used for product recovery, then separation efficiency improves, but operational costs increase

Engineering Contradiction:
Improveseparation efficiencyVSAvoidoperational cost
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent employs a disposable flow chamber that contains the acoustophoretic separation mechanism. Instead of maintaining expensive, complex filtration systems that require cleaning and maintenance, the entire flow chamber can be discarded after use, reducing operational costs while maintaining high separation efficiency through the acoustic field generated by the ultrasonic transducer.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Quantity of substance

If cell retention devices are implemented in perfusion bioreactors, then cell density increases, but operational reliability decreases due to malfunction risks

Engineering Contradiction:
Improvecell densityVSAvoidoperational reliability
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent replaces mechanical cell retention devices with an acoustophoretic separation system that uses acoustic standing waves to trap cells at nodes. This non-mechanical approach eliminates moving parts and complex valve systems that are prone to malfunction, thereby improving operational reliability while maintaining the ability to achieve high cell densities through continuous perfusion.

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 approach significantly reduces the cost and effort of bioreactor operations by efficiently separating cells and cell debris from biomolecules, minimizing product loss and enhancing bioreactor productivity, while also being applicable in various bioreactor modes including perfusion and fed-batch processes.

Implementation Method 1

at least one ultrasonic transducer located on a wall of the flow chamber, the transducer including a piezoelectric material driven by a voltage signal to create a multi-dimensional acoustic standing wave in the flow chamber

Methodology Applied
Scientific EffectAcoustic standing waves: Sound

Implementation Method 2

high intensity standing waves of sound can exert forces on particles in a fluid when there is a differential in both density and/or compressibility, otherwise known as the acoustic contrast factor

Methodology Applied
Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Implementation Method 3

A thin structure is located on the wall on the opposite side of the flow chamber from the at least one ultrasonic transducer. The thin structure provides a pressure release boundary that acts as a reflector

Methodology Applied
Scientific EffectAcoustic reflection: Reflection

Implementation Method 4

the transducer including a piezoelectric material driven by a voltage signal to create a multi-dimensional acoustic standing wave in the flow chamber

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 5

allowing for efficient clustering and gravity separation without the need for traditional filtration methods

Methodology Applied
Scientific EffectGravity: Gravitation

Data Source

PatentUS9623348B2Reflector for an acoustophoretic device
Publication Date: 2017.04.18 FLODESIGN SONICS INC
  • US9623348B2 patent drawing
  • US9623348B2 patent drawing
  • US9623348B2 patent drawing

AI summary

An apparatus includes a flow chamber having at least one inlet and at least one outlet. At least one ultrasonic transducer is located on a wall of the flow chamber, which operates to create a multi-dimensional acoustic standing wave in the flow chamber. A reflector is located on the wall on the opposite side of the flow chamber from the at least one ultrasonic transducer. The reflector is formed from a thin structure that provides a pressure release boundary, such as a plastic film/air interface.