Multi-reactor Bioreactor with Detachable Connectors for Sampling

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Solution Overview

Problem

Current bioreactor systems for dynamic cellular culture face challenges such as complex and time-consuming sampling procedures, risk of metabolic marker concentration changes due to adsorption, and inefficient cell insemination processes, which affect the accuracy of toxicology tests and increase operational costs.

Innovation Solution

A multi-bioreactor box with microstructured chambers connected via detachable connectors allows for in-situ sampling and reduced circuit length, eliminating the need for external tanks and bubble traps, enabling precise sampling and efficient cell insemination with minimal handling and reduced risk of bubble destruction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If parallel bioreactors are used to increase cell culture surface area, then productivity is improved, but device complexity increases due to multiple connectors and extended perfusion circuits

Engineering Contradiction:
Improvecell culture surface areaVSAvoidperfusion circuit complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The device divides the cell culture system into multiple independent microstructured chambers (bioreactors) that can be cultured in parallel, thereby increasing the total cell culture surface area while maintaining manageable complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A single perfusion circuit is designed to serve multiple bioreactors simultaneously, with the circuit capable of distributing nutritive medium to and collecting effluent from several chambers through a unified connector system, reducing overall circuit complexity

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

2Quantity of substance

If sampling is performed in an external tank, then sampling capacity is improved, but loss of time occurs due to halting fluid perfusion and complex sampling procedures

Engineering Contradiction:
Improvesampling capacityVSAvoidsampling operation time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The sampling function is extracted from the external tank and integrated directly into each bioreactor chamber through dedicated sampling ports, allowing samples to be taken in-situ without requiring the system to halt perfusion or use separate sampling equipment

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Each bioreactor chamber is equipped with its own sampling port that enables independent sampling operations, allowing the system to perform sampling functions autonomously during continuous operation without external intervention or circuit interruption

Inventive Principle:
Principle #25Self-service

3Reliability

If long perfusion circuits with external tanks and bubble traps are used, then reliability is improved by preventing bubble formation, but loss of substance occurs due to adsorption of chemical substances on pipe surfaces

Engineering Contradiction:
Improvebubble preventionVSAvoidchemical substance concentration
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

External tanks and bubble traps are removed from the perfusion circuit, with bubble prevention functionality integrated directly into the microstructured chambers through designed outlet configurations that enable automatic debubbling at the source rather than requiring separate external components

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system transitions from extended one-dimensional perfusion circuits to compact three-dimensional microstructured chambers, dramatically reducing the total surface area of contact between the nutritive medium and pipe walls, thereby minimizing adsorption losses while maintaining effective bubble trapping through vertical outlet design

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

4Reliability

If thick plates with hole-based connectors are used for bioreactor assembly, then sealing is improved, but ease of operation deteriorates during cell insemination due to redundant operations

Engineering Contradiction:
Improvesealing qualityVSAvoidcell insemination efficiency
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The connector structure integrates multiple functions into a single component: it provides sealing through its design, serves as the access point for cell insemination, and enables fluidic connections, thereby eliminating the need for separate sealing elements and reducing redundant operations during maintenance and inoculation

Inventive Principle:
Principle #5Merging (Combining)

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 solution enables reliable, high-precision sampling and rapid, economical cellular insemination, improving the accuracy of toxicology tests and reducing operational time and costs by allowing for continuous perfusion and automatic debubbling, while enabling visual monitoring of cell proliferation.

Implementation Method 1

Bioreactors comprise at both ends of a microstructured chamber (a culture chamber comprising an upper wall and a lower wall having microstructures) a point of entry for fluid and an outlet point for fluid to allow passage of nutritive fluid necessary for the development of cells. The fluid is therefore in circulation, propelled for example by a pump

Methodology Applied
Scientific EffectFluid circulation:

Implementation Method 2

The microstructured chamber is connected fluidically at inlet and/or at outlet by a set of connectors inserted detachably into a hole of the upper plate

Methodology Applied
Scientific EffectFluid connection:

Implementation Method 3

This solution enables reliable, high-precision sampling and rapid, economical cellular insemination, improving the accuracy of toxicology tests and reducing operational time and costs by allowing for continuous perfusion

Methodology Applied
Scientific EffectSampling:

Implementation Method 4

enabling visual monitoring of cell proliferation... by allowing for continuous perfusion and automatic debubbling

Methodology Applied
Scientific EffectBubble removal:

Data Source

PatentUS10119112B2Multi-reactor unit for dynamic cell culture
Publication Date: 2018.11.06 UNIV DE TECH DE COMPIEGNE UTC
  • US10119112B2 patent drawing
  • US10119112B2 patent drawing
  • US10119112B2 patent drawing

AI summary

The present invention relates to a unit (1) comprising a microsystem (150) and at least one set of interface connections (16) for the microsystem (150); the microsystem (150) comprising a bottom plate (152) bearing the impression of at least one microstructured dynamic cell culture chamber (15), and a top plate (151), characterized in that the at least one microstructured chamber (15) is fluidically connected at inlet and/or at outlet by a set of connections (16) inserted removably into a hole in the upper plate (151). The present invention also relates to a dynamic cell culture system to this effect.