Segmented Bio-reactor for Gradient-Free Cell Cultivation

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Solution Overview

Problem

Current bio-reactor designs face challenges in scaling from bench-top to industrial production without generating undesirable gradients, limiting the scalability and efficiency of stem cell and micro organism cultivation, and requiring costly and time-consuming cleaning processes.

Innovation Solution

A bio-reactor design featuring permeable discs or envelopes with interconnected open pores and a matrix structure that allows for gradient-free nutrient and oxygen distribution, enabling efficient cultivation of biological cells at high densities, and a single-use, disposable setup to reduce manufacturing costs and eliminate cleaning requirements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If bed thickness is increased to increase cultivation volume, then productivity is improved, but gradients in nutrient and oxygen distribution are generated

Engineering Contradiction:
Improvecultivation volumeVSAvoidgradient-free distribution
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The packed bed is divided into multiple thin layers (each less than 2 cm thick) separated by permeable spacers. This segmentation allows nutrient and oxygen distribution to be maintained uniformly across each layer while achieving large overall cultivation volume through stacking multiple layers, thus resolving the contradiction between productivity and gradient-free distribution.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from a single thick bed to a multi-layer stacked structure, adding the vertical dimension of layering. This dimensional change allows the system to achieve large volume through multiple thin layers rather than one thick layer, eliminating gradients while maintaining productivity.

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

2Productivity

If agitation speed is increased to improve oxygen transfer and mixing, then productivity is improved, but power consumption increases and cell damage occurs

Engineering Contradiction:
Improveoxygen transferVSAvoidpower consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The invention replaces mechanical agitation with a passive mass transfer system using thin packed bed layers and permeable spacers that enable efficient oxygen and nutrient distribution without mechanical movement. This substitution eliminates the need for high-power agitation while maintaining effective oxygen transfer and avoiding cell damage.

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

3Productivity

If reactor volume is increased for industrial production, then productivity is improved, but gradient problems increase and scalability is limited

Engineering Contradiction:
Improvemass production capacityVSAvoidenvironmental condition uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The large-scale reactor is segmented into multiple thin layers stacked vertically, with each layer maintaining uniform environmental conditions. This segmentation allows industrial-scale productivity while preventing gradient problems that would occur in a single large-volume reactor.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention scales up production by adding vertical layering rather than increasing horizontal reactor volume. This dimensional approach allows industrial-scale capacity while maintaining uniform environmental conditions in each thin layer, achieving scalability without gradient problems.

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

4Loss of substance

If reusable reactor design is used to reduce costs, then loss of substance is reduced, but cleaning and validation time increases

Engineering Contradiction:
Improvemedia lossVSAvoidcleaning and validation time
Core Design Contradiction:
Loss of substanceVSLoss of time

Solution Approach 1:

The invention employs disposable single-use packed beds that are discarded after one use. This approach eliminates the need for time-consuming cleaning and validation processes while the low cost of disposable units offsets the theoretical loss of expensive media, resolving the contradiction between substance loss and time loss.

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

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 bio-reactor achieves scalable, gradient-free operation, supporting high cell densities and efficient production of biologics, while reducing equipment volume and costs through a compact, single-use design that eliminates the need for extensive cleaning and validation processes.

Implementation Method 1

A bio-reactor design featuring permeable discs or envelopes with interconnected open pores and a matrix structure that allows for gradient-free nutrient and oxygen distribution

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS9677038B2Device and method for industrial cultivation of cells
Publication Date: 2017.06.13 STOBBE GMBH
  • US9677038B2 patent drawing
  • US9677038B2 patent drawing
  • US9677038B2 patent drawing

AI summary

A compact, high-yield, bio-reactor for use as small, medium and large-scale production unit for hosting and culturing of stem cells or living cells or micro organism and producing by multiplication or expression one or more biologic compounds for medical and biological applications.