Micro-bioreactor Gas Spacer for Long-Term Culture Stability

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Solution Overview

Problem

Existing methods for confining microorganisms in micro-bioreactors fail to maintain the integrity of the system beyond 24 hours, as the growth or biological activity of microorganisms can cause reservoirs to merge or subdivide, leading to inaccurate results due to changes in metabolite concentration and loss of referencing.

Innovation Solution

The use of a capillary tube with a carrier fluid transporting a train of micro-bioreactors separated by a gas spacer fluid, where the micro-bioreactors are smaller than the capillary tube, and the spacer fluid is a gas such as air or a nitrogen/carbon dioxide mixture, ensuring stability and preventing contamination and self-emulsification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If liquid spacer fluid is used to separate micro-bioreactors, then the micro-bioreactors can be effectively separated and transported, but the integrity of the reservoirs is lost beyond 24 hours due to merging or subdivision caused by microorganism growth and biological activity

Engineering Contradiction:
Improveintegrity of reservoirsVSAvoidincubation time
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent changes the physical state parameter of the spacer fluid from liquid to gas. This parameter change fundamentally alters the interaction between the spacer fluid and microorganisms, preventing biological activity from compromising reservoir integrity. The gas spacer fluid maintains physical separation without providing a liquid medium that could support microbial growth or allow interface modification that leads to merging or subdivision.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The gas spacer fluid acts as an intermediary substance between micro-bioreactors. It provides mechanical separation and prevents direct contact between adjacent culture droplets, while its gaseous nature ensures it does not support microbial growth or allow interface modification. This intermediary maintains reservoir integrity over extended periods without interfering with microorganism cultivation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If micro-bioreactors are confined in a capillary tube with liquid spacer fluid, then kinetic monitoring can be performed, but accurate measurement is compromised when reservoir size varies due to merging or subdivision

Engineering Contradiction:
Improvemetabolite concentration measurementVSAvoidreservoir size stability
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

Changing the spacer fluid from liquid to gas stabilizes the physical dimensions of micro-bioreactors. The gas phase cannot be modified by microbial metabolic activities in the way liquid can, preventing changes in reservoir size that would otherwise occur through merging or subdivision. This ensures consistent measurement conditions throughout the incubation period.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The gas spacer fluid provides a stable, non-reactive environment that prevents the need for frequent system replacement or recalibration. By maintaining reservoir integrity without liquid-induced merging or subdivision, the system achieves long-term measurement accuracy without requiring intervention or system redesign.

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

3Reliability

If the diameter of micro-bioreactors is reduced to prevent filamentous fungus obstruction, then the train stability is improved, but the contact surface with capillary increases leading to more edge effects

Engineering Contradiction:
Improvetrain stabilityVSAvoidedge effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the spacer fluid phase from liquid to gas, which fundamentally alters the boundary conditions at the micro-bioreactor interfaces. The gas-liquid interface created by the gas spacer reduces surface tension effects and minimizes edge effects at the capillary wall interfaces, while the gaseous nature prevents filamentous fungus obstruction issues that plague liquid systems.

Inventive Principle:
Principle #35Parameter changes

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 allows for the long-term monitoring of microorganism growth and biological activities, maintaining the integrity of the system and providing accurate kinetic data over extended periods, with maximum incubation times exceeding previous limits.

Implementation Method 1

said micro-bioreactors are separated by a spacer fluid, the latter being a gas

Methodology Applied
Scientific EffectGas-liquid immiscibility:

Implementation Method 2

a capillary tube in which circulates a carrier fluid intended to advance a train of drops consisting of micro-bioreactors

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 3

said carrier fluid (7) allowing both to move the drops and to lubricate the capillary (8), avoiding contamination between consecutive drops (5)

Methodology Applied
Scientific EffectLubrication: Lubrication

Implementation Method 4

the use of a gas as spacer fluid is enough to solve the problem of self-emulsification

Methodology Applied
Scientific EffectGas barrier:

Data Source

PatentEP3019590B8Novel method for cultivating micro-organisms by confinement in micro-bioreactors
Publication Date: 2017.09.27 ETABLISSEMENTS J SOUFFLET

AI summary

The present invention relates to a novel method for cultivating micro-organisms by confinement in micro-bioreactors. Said method comprises using a capillary tube in which a carrier fluid for moving a train of droplets forward flows, said capillary tube comprising micro-bioreactors in which the culture of said micro-organisms takes place, wherein said micro-bioreactors are separated by a spacing fluid which is a gas. The diameter of the micro-bioreactors (5) is smaller than that of the capillary tube (8) and the size of the bubble (6) of said spacing fluid is within a range of two to ten times the diameter of said capillary tube (8). The method can be used for cultivating micro-organisms such as thread-like fungi or planktonic algae.