Microfluidic Bio-Reactor with Gas Permeable Air-Bubble Removal

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Solution Overview

Problem

Conventional microfluidic devices for cell culture face issues such as uneven cell distribution, air-bubble formation, and inadequate nutrient supply, which affect cell growth and differentiation, and are not suitable for mass production due to limited culture chamber size or excessive device volume.

Innovation Solution

A microfluidic bio-reactor device with an open-cover design achieved through negative pressure, featuring a microfluidic base with channels and holes, a gas-permeable layer for air-bubble removal, and a vacuum channel to ensure homogeneous cell distribution and long-term culture, utilizing polydimethylsiloxane (PDMS) and glass components for the cell culture layers and roof, respectively.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If cells are injected through seeding microchannels, then cells can be delivered into the culture chamber, but uneven cell distribution occurs which affects cellular interaction and differentiation

Engineering Contradiction:
Improvecell deliveryVSAvoidcell distribution uniformity
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The device segments the culture chamber into multiple regions with different functions: a culture chamber for cell growth, a waste chamber for removing unhealthy cells and air bubbles, and a seeding channel for cell introduction. This segmentation allows cells to be delivered efficiently while maintaining uniform distribution in the culture chamber by separating the delivery pathway from the growth area.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A gas permeable layer is introduced as an intermediary component between the culture chamber and waste chamber. This layer allows air bubbles to pass through while retaining cells, enabling the removal of harmful air bubbles without affecting cell distribution or growth in the culture chamber.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Duration of action of stationary object

If the device is sealed for long-term culture, then cell culture can be maintained, but air bubbles cannot be removed which affects cell growth

Engineering Contradiction:
Improveculture durationVSAvoidair bubble presence
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

A gas permeable layer is introduced as an intermediary component between the culture chamber and waste chamber. This layer allows air bubbles to pass through while retaining cells, enabling the removal of harmful air bubbles without affecting cell distribution or growth in the culture chamber.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The device extracts air bubbles from the culture system by directing them through the gas permeable layer into the waste chamber, where they can be removed. This extraction process maintains the sealed environment for long-term culture while eliminating harmful air bubbles that would otherwise affect cell growth.

Inventive Principle:
Principle #2Taking out (Extraction)

3Productivity

If the culture chamber area is increased for mass production, then cell production capacity improves, but device volume becomes too large

Engineering Contradiction:
Improvecell production capacityVSAvoiddevice volume
Core Design Contradiction:
ProductivityVSVolume of stationary object

Solution Approach 1:

The device utilizes vertical stacking to create multiple culture chambers above and below the main culture chamber. This dimensional expansion allows increased cell production capacity without proportionally increasing the device's footprint area, maintaining a compact form factor while enhancing productivity.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

Multiple culture chambers are nested within a compact device structure, with chambers positioned at different vertical levels. This nesting arrangement maximizes the use of three-dimensional space, allowing large total culture area while maintaining a small overall device volume suitable for mass production applications.

Inventive Principle:
Principle #7Nested doll (Nesting)

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 device enables rapid and uniform cell growth, prevents air-bubble formation, and supports large-scale cell culture, maintaining cell properties and allowing for easy removal of unhealthy cells, thereby facilitating efficient stem cell culture and mass production.

Implementation Method 1

a gas permeable layer, wherein the first end of the air-bubble removal device is connected to the gas permeable layer

Methodology Applied
Scientific EffectGas permeability: Permeation

Implementation Method 2

an air-bubble removal device, which is a vacuum channel, having a first end and a second end, wherein the first end of the air-bubble removal device is connected to the gas permeable layer and the second end of the air-bubble removal device is connected to a vacuum opening

Methodology Applied
Scientific EffectVacuum: Vacuum

Data Source

PatentUS10106766B2Microfluidic bio-reactor device
Publication Date: 2018.10.23 NAT YANG MING CHIAO TUNG UNIV
  • US10106766B2 patent drawing
  • US10106766B2 patent drawing
  • US10106766B2 patent drawing

AI summary

The present invention provides a microfluidic bio-reactor device, which comprises: a first cell culture layer; a microfluidic base, which is located on the top of the first cell culture layer; a microfluidic layer, which is located on the top of the microfluidic base and have an air-bubble removal device; a microfluidic roof, which is located on the top of the microfluidic layer; the present invention also provides a method for culturing cells by the microfluidic bio-reactor device of the present invention and the kit with a cell-loading device and present microfluidic bio-reactor device.