Microfluidic Apparatus for Bubble-Cell Distance Control

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Solution Overview

Problem

Existing devices for acoustic perforation in gene therapy cannot precisely control the distance between ultrasonic contrast bubbles and cells, leading to unstable shear stress and inefficient introduction of substances into cells.

Innovation Solution

A microfluidic apparatus with a cavity channel, bulk wave generating device, and surface acoustic wave generating device is used to create a controlled flow field, allowing precise positioning of cells relative to the bubble, thereby controlling the shear stress and forming reversible pores in the cell membrane for substance introduction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the distance between the bubble and the cell is increased, then the cell membrane integrity is maintained, but the opening efficiency of the cell membrane decreases

Engineering Contradiction:
Improvecell membrane integrityVSAvoidopening efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent employs dynamic control of bubble-cell distance through acoustic standing waves, allowing the system to adjust the position of bubbles relative to cells in real-time. The acoustic field creates a controllable dynamic environment where the bubble-cell distance can be precisely modulated to achieve optimal transfection conditions without permanent damage to cells.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the physical parameters of the acoustic field (frequency, amplitude, standing wave patterns) to control bubble behavior and position. By adjusting these parameters, the system can optimize the bubble-cell interaction distance to achieve high opening efficiency while maintaining cell membrane integrity through precise parameter control.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If the distance between the bubble and the cell is decreased, then the opening efficiency of the cell is improved, but the shear stress may cause cell separation and lethal damage

Engineering Contradiction:
Improveopening efficiencyVSAvoidshear stress damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The acoustic standing wave field creates a dynamic control mechanism where bubbles can be positioned at specific nodes or antinodes relative to cells. This dynamic positioning allows the system to achieve close bubble-cell proximity for high opening efficiency while controlling the duration and intensity of shear stress exposure to prevent lethal damage.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent utilizes periodic acoustic waves to create oscillating bubble behavior. The periodic nature of the acoustic field allows bubbles to approach cells at controlled intervals, creating repeated low-level shear stress exposure that accumulates sufficient opening efficiency without causing lethal damage from continuous high-level stress.

Inventive Principle:
Principle #19Periodic action

3Productivity

If conventional acoustic perforation devices are used, then substance introduction into cells can be achieved, but the distance between bubble and cell cannot be precisely controlled

Engineering Contradiction:
Improvesubstance introduction capabilityVSAvoidbubble-cell distance control
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent implements feedback control through the acoustic field, where the standing wave pattern provides inherent position information for bubbles. The system can detect and respond to bubble positions by adjusting acoustic parameters, creating a feedback loop that precisely controls bubble-cell distance and maintains optimal transfection conditions.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent replaces mechanical positioning systems with acoustic field-based positioning. Instead of using mechanical devices to physically position bubbles and cells, the system uses acoustic standing waves to create virtual positioning, achieving precise distance control through wave mechanics rather than mechanical means.

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 enables accurate control of particle position and shear stress, enhancing the efficiency and safety of substance introduction into cells by forming reversible pores at optimal positions, improving the delivery of therapeutic agents like genes or drugs.

Implementation Method 1

the bulk wave generating device is configured to generate a bulk wave, so that the bulk wave enables the bubble to resonate for generating a flow field

Methodology Applied
Scientific EffectBulk wave: Ultrasound

Implementation Method 2

the surface acoustic wave generating device is configured to generate a surface acoustic wave and control a position of at least one particle in the solution

Methodology Applied
Scientific EffectSurface acoustic wave: Surface Acoustic Wave

Implementation Method 3

the bubbles generate a cavitation effect under an action of the ultrasonic waves, which causes physical phenomena, such as expansion, implosion, a micro sound flow, a micro jet flow, a shock wave and etc.

Methodology Applied
Scientific EffectCavitation: Cavitation

Implementation Method 4

the mixed solution is exposed to an ultrasonic wave, the bubbles generate a cavitation effect under an action of the ultrasonic waves

Methodology Applied
Scientific EffectUltrasonic wave: Ultrasound

Implementation Method 5

a microstructure is arranged on an inner wall of the cavity channel, and the microstructure is constructed for forming a bubble by a solution at the microstructure when the solution is injected into the cavity channel

Methodology Applied
Scientific EffectBubble formation: Bubble

Data Source

PatentUS11511277B2Microfluidic apparatus, and system and method for introducing substance into cell
Publication Date: 2022.11.29 SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
  • US11511277B2 patent drawing
  • US11511277B2 patent drawing
  • US11511277B2 patent drawing

AI summary

Provided are a microfluidic apparatus, a method and system for introducing a substance into a cell. The microfluidic apparatus includes a cavity channel, a bulk wave generating device and a surface acoustic wave generating device; a microstructure is arranged on an inner wall of the cavity channel, and the microstructure is constructed for forming a bubble by a solution at the microstructure when the solution is injected into the cavity channel; the bulk wave generating device is configured to generate a bulk wave, the bulk wave enables the bubble to resonate for generating a flow field; and the surface acoustic wave generating device is configured to generate a surface acoustic wave and control a position of at least one particle in the solution.