Hollow Fiber Bioreactor Cell Distribution via Flow Control

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Solution Overview

Problem

Hollow fiber bioreactors face challenges in evenly distributing cells throughout the length and width of the fibers, leading to uneven growth and inefficiencies in cell expansion.

Innovation Solution

A method involving fluid flow at controlled pressure rates to move and distribute cells within the intracapillary and extracapillary spaces of hollow fiber bioreactors, using semi-permeable membranes to facilitate nutrient transfer and waste removal, and employing pumps and valves to regulate fluid flow for optimal cell distribution and reseeding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If cells are loaded into hollow fiber bioreactors using conventional methods, then cells can be introduced into the bioreactor, but cells are not properly distributed throughout the length and width of the hollow fibers, leading to uneven growth

Engineering Contradiction:
Improvecell distribution uniformityVSAvoidcell expansion efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The system dynamically switches between different flow modes (fill mode with high flow rate, growth mode with low flow rate) to achieve both proper cell distribution and efficient cell expansion. The flow rate is adjusted based on the operational phase to optimize both distribution uniformity and productivity

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes the flow rate parameter from high during cell loading to low during cell growth. This parameter change enables cells to be properly distributed during the filling phase and then maintains uniform growth during the expansion phase, resolving the contradiction between distribution precision and expansion efficiency

Inventive Principle:
Principle #35Parameter changes

2Loss of time

If high flow rate is used to distribute cells quickly, then cell loading time is reduced, but cells may not properly settle and distribute throughout the fibers

Engineering Contradiction:
Improvecell loading timeVSAvoidcell distribution uniformity
Core Design Contradiction:
Loss of timeVSManufacturing precision

Solution Approach 1:

The system performs a preliminary high flow rate filling operation to quickly load cells into the hollow fibers, then switches to a low flow rate growth mode to allow cells to properly settle and distribute. This preliminary action followed by a stabilization phase resolves the contradiction between speed and precision

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention uses periodic switching between high flow rate (fill mode) and low flow rate (growth mode) to achieve both rapid cell loading and proper cell distribution. The periodic alternation allows the system to capture the benefits of both high and low flow rates at different stages

Inventive Principle:
Principle #19Periodic action

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 method ensures uniform cell distribution and growth along the entire length of the fibers, enhancing the efficiency of cell expansion and harvesting processes while minimizing the loss of essential growth factors.

Implementation Method 1

The hollow fibers are comprised of a semi-permeable membrane that allows for the transfer of nutrients from the extracapillary space to the intracapillary space where the cells are grown

Methodology Applied
Scientific EffectPermeation: Permeation

Implementation Method 2

flowing a fluid into one of the intracapillary space or extracapillary space at a flow rate pressure to move and distribute the cells along a length of the fibers

Methodology Applied
Scientific EffectPressure gradient: Pressure Gradient

Data Source

PatentEP2115116B1Methods to control cell movement in hollow fiber bioreactors
Publication Date: 2018.01.24 TERUMO BCT INC
  • EP2115116B1 patent drawingFigure 1
  • EP2115116B1 patent drawingFigure 2

AI summary

This invention is directed toward methods of moving cells throughout a hollow fiber bioreactor using fluid flow.