Acoustic Pressure Transient Cell Permeabilization

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Solution Overview

Problem

Current methods for introducing exogenous materials into cells, such as nucleic acids, are often inefficient, costly, and can be harsh on cells, leading to low viability and high mortality rates, and are not adaptable to high-throughput applications.

Innovation Solution

Exposing cells to a transient decrease in pressure in the presence of exogenous materials, which temporarily permeabilizes the cell membrane without lysing the cell, allowing for efficient uptake of various materials like nucleic acids, proteins, and nanoparticles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional transfection methods (chemical, physical, viral) are used to introduce exogenous material into cells, then transfection efficiency can be improved, but cell mortality increases and cell viability decreases

Engineering Contradiction:
Improvetransfection efficiencyVSAvoidcell mortality
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces conventional mechanical transfection methods (electroporation, microinjection, sonication) with a chemical-free, physics-based approach using acoustic waves and pressure differentials. This substitution eliminates mechanical damage to cells while maintaining transfection efficiency, directly resolving the contradiction between high transfection efficiency and low cell mortality.

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

Solution Approach 2:

The patent utilizes controlled changes in pressure parameters (positive and negative pressure differentials) and acoustic wave parameters (frequency, amplitude, duration) to create transient membrane permeability. By precisely controlling these physical parameters, the method achieves efficient transfection while keeping cell mortality low, as the parameters are optimized to be sufficient for membrane permeabilization but not excessive to cause cell lysis.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If chemical transfection reagents are used to package nucleic acids for delivery, then transfection efficiency can be improved, but the cost increases and cell toxicity increases

Engineering Contradiction:
Improvetransfection efficiencyVSAvoidcell toxicity
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and eliminates chemical transfection reagents (liposomes, polymers, dendrimers) from the transfection process entirely. By removing these chemical components and replacing them with a purely physical method (acoustic wave-induced pressure differentials), the invention achieves transfection efficiency without the associated cell toxicity and cost issues.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces expensive chemical reagents with a cost-effective physical method using acoustic waves and pressure differentials. The method uses no consumable reagents that need to be purchased and disposed of, significantly reducing the cost per transfection while eliminating the toxic effects of chemical reagents on cells.

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

3Productivity

If conventional transfection methods are used, then some level of transfection efficiency can be achieved, but the method is not adaptable to high-throughput applications

Engineering Contradiction:
Improvetransfection efficiencyVSAvoidhigh-throughput adaptability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal transfection method using acoustic waves and pressure differentials that can be applied to various cell types (suspended, adherent, 3D cultures) and various exogenous materials (nucleic acids, proteins, nanoparticles) without requiring method optimization. This universality enables high-throughput applications across different cell types and materials, resolving the contradiction between achieving transfection efficiency and adapting to high-throughput workflows.

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

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 achieves high efficiency and viability of cell transfection with minimal cell mortality, enabling scalable and cost-effective introduction of exogenous materials into a range of cell types, including mammalian and bacterial cells.

Implementation Method 1

exposing the cell to a transient decrease in pressure in the presence of the exogenous material

Methodology Applied
Scientific EffectPressure decrease: Pressure Drop

Implementation Method 2

temporarily permeabilizes the cell membrane without lysing the cell

Methodology Applied
Scientific EffectPermeabilization: Permeation

Implementation Method 3

an unsteady flow of liquid in which the cell and exogenous material are present

Methodology Applied
Scientific EffectUnsteady flow: Turbulence

Data Source

PatentUS11306284B2Method for mechanical and hydrodynamic microfluidic transfection
Publication Date: 2022.04.19 INDEE INC
  • US11306284B2 patent drawing
  • US11306284B2 patent drawing
  • US11306284B2 patent drawing

AI summary

Methods for introducing exogenous material into a cell are provided, which include exposing the cell to a transient decrease in pressure in the presence of the exogenous material. Also provided are devices for performing the method of the invention.