Frustoconical Cell Growth Chamber with Gravity-Driven Media Reservoir

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Solution Overview

Problem

Existing cell expansion systems face challenges in achieving high density non-adherent cell growth, as the availability of cell growth media significantly influences cell expansion and density, with current technologies not efficiently providing the necessary environment for optimal growth.

Innovation Solution

A closed cell expansion system comprising a cell growth chamber with a specialized frustoconical shape, a mass transfer device, and a fluid circulation loop, where gravitational forces cause cells to settle in a media-rich reservoir, and a semi-permeable membrane allows for nutrient and oxygen exchange, maintaining cells in suspension and promoting high density growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a large volume of cell growth media is provided to promote increased cell growth, then cell density and growth are improved, but the complexity of the system and difficulty of media management increase

Engineering Contradiction:
Improvecell growth densityVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system divides the cell growth chamber into multiple compartments separated by semi-permeable membranes, allowing independent control of media volume in each section while maintaining overall system functionality. This segmentation enables optimized media distribution without requiring a single large complex volume.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements a nested structure where smaller cell growth chambers are positioned within a larger outer chamber, with media flowing from the outer chamber through semi-permeable membranes into the inner chambers. This nesting allows efficient use of media volume while maintaining manageable system complexity through hierarchical organization.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Productivity

If cells are maintained in suspension to enable non-adherent growth, then cell expansion is improved, but the stability of cell distribution and media homogeneity deteriorates

Engineering Contradiction:
Improvecell expansionVSAvoidcell distribution stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The system employs dynamic media circulation patterns where media flows continuously through the chambers, preventing static settling while maintaining suspension. The semi-permeable membranes allow dynamic exchange of media and cells, ensuring stable cell distribution through controlled movement rather than static containment.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent utilizes fluid dynamics and pressure gradients to maintain cell suspension and media homogeneity. By controlling media flow rates and pressure differentials across the semi-permeable membranes, the system keeps cells evenly distributed in suspension without requiring mechanical agitation, thus maintaining stability while enabling expansion.

Inventive Principle:
Principle #29Pneumatics and hydraulics

3Productivity

If a specialized frustoconical chamber shape is used to utilize gravity for media-rich reservoir creation, then cell growth efficiency is improved, but the difficulty of manufacturing and device complexity increase

Engineering Contradiction:
Improvecell growth efficiencyVSAvoidchamber manufacturing
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent modifies the chamber geometry parameters, specifically using a frustoconical shape with specific angle ranges and dimensional ratios, to optimize gravity-driven media distribution. By carefully selecting geometric parameters within defined ranges, the system achieves improved cell growth efficiency while maintaining manufacturability through standardized forming processes.

Inventive Principle:
Principle #35Parameter changes

4Productivity

If semi-permeable membranes are used for nutrient and oxygen exchange, then media exchange efficiency is improved, but the loss of cells through the membrane and manufacturing precision requirements worsen

Engineering Contradiction:
Improvenutrient exchange efficiencyVSAvoidcell loss
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The system employs semi-permeable membranes with specifically controlled pore sizes and porous structures that allow selective passage of nutrients, gases, and waste products while blocking cells. The porous material properties are optimized to maximize exchange efficiency while minimizing cell leakage, achieving high productivity with minimal cell loss.

Inventive Principle:
Principle #31Porous materials

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 system efficiently promotes high density non-adherent cell growth by maintaining cells in a media-rich environment, allowing for optimal nutrient and waste exchange, and accommodating different cell types and sizes through the cumulative features of the chamber, mass transfer device, and fluid circulation loop.

Implementation Method 1

By vertically positioning the cell growth chamber, gravitational forces cause cells to accumulate in the lower portion of the cell growth chamber

Methodology Applied
Scientific EffectGravity: Gravitation

Implementation Method 2

The circulating media is replenished by nutrients and oxygen diffusing through the extracapillary space into the intracapillary space

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 3

Waste in the circulating media may also be diffused from the media into the extracapillary space

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP2710118B1Systems and methods for expanding high density non-adherent cells
Publication Date: 2018.02.07 TERUMO BCT INC
  • EP2710118B1 patent drawingFigure 1
  • EP2710118B1 patent drawingFigure 2
  • EP2710118B1 patent drawingFigure 3

AI summary

Embodiments described herein generally relate to systems and methods for promoting the expansion of high density non-adherent cells through the use of a cell growth chamber, a mass transfer device, and a fluid circulation loop. Improved cell growth is achieved in the cell growth chamber by using a chamber having a particular orientation and shape, e.g., conical, to create a media-rich reservoir for growing cells. By placing the chamber in a vertical position, the force of media flow along the chamber walls is substantially equal and opposite to the gravitational force on the cells. The interaction of these forces maintains the non-adherent cells in suspension. The use of the cell growth chamber in conjunction with the mass transfer device and fluid circulation loop(s) creates efficiencies by relying on the cumulative and combined features of the devices.