Bioreactor Cyclic Negative Pressure Blood Cell Production

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current bioreactor systems fail to replicate the tissue conditions necessary for effective blood cell production, particularly in mimicking the pressure differential between tissue interstitial pressure and venular pressure, which is crucial for cultivating red blood cells extracorporeally.

Innovation Solution

A bioreactor system that includes a reaction chamber with a hydrodynamic apparatus generating a cyclic negative pressure differential, simulating the pressure conditions found in bone marrow tissue by creating a slow constant negative pressure gradient and oscillating pressure, allowing for the cultivation and collection of blood cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current bioreactor systems are used for blood cell production, then cell cultivation can be performed, but the pressure differential between tissue interstitial pressure and venular pressure is not replicated, resulting in ineffective blood cell production

Engineering Contradiction:
Improveblood cell production effectivenessVSAvoidability to mimic tissue pressure conditions
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The bioreactor system employs a dynamic pressure control mechanism that actively adjusts and maintains a pressure differential between the tissue culture chamber and venular outflow chamber, mimicking the natural physiological conditions in bone marrow. This dynamic pressure regulation enables effective blood cell production by replicating the interstitial-to-venular pressure gradient that drives hematopoiesis in vivo.

Inventive Principle:
Principle #15Dynamics

2Reliability

If a cyclic negative pressure differential is generated to simulate bone marrow conditions, then blood cell production effectiveness is improved, but device complexity increases

Engineering Contradiction:
Improveblood cell production effectivenessVSAvoidhydrodynamic apparatus complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The bioreactor system implements periodic cyclic negative pressure fluctuations that simulate the natural pulsatile blood flow and pressure variations in bone marrow vasculature. This periodic pressure application enhances blood cell production by mimicking physiological stimuli that regulate hematopoiesis, while the cyclic nature of the pressure changes can be achieved through relatively simple pump or piston mechanisms.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The system uses pneumatic or hydraulic pressure control mechanisms to generate and regulate the cyclic negative pressure differential. By employing fluid pressure systems rather than complex mechanical structures, the bioreactor achieves physiologically relevant pressure conditions with relatively simple and controllable apparatus, balancing device complexity with functional effectiveness.

Inventive Principle:
Principle #29Pneumatics and hydraulics

3Ease of manufacture

If extracorporeal blood cell cultivation is performed without proper pressure differential, then economic and safe production may be achieved, but cell production effectiveness is reduced

Engineering Contradiction:
Improveeconomic and safe productionVSAvoidblood cell production rate
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The bioreactor system is designed to automatically maintain the pressure differential and cyclic pressure fluctuations required for effective blood cell production, reducing the need for complex manual intervention or monitoring. This self-regulating pressure control mechanism enables safe and economical extracorporeal cultivation while maintaining high productivity, as the system autonomously replicates physiological conditions without requiring constant operator adjustment.

Inventive Principle:
Principle #25Self-service

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 enables the safe and economic cultivation of blood cells by duplicating the marrow tissue conditions, facilitating the production and collection of red blood cells and other hematopoietic cells, addressing the limitations of existing bioreactor systems.

Implementation Method 1

A bioreactor system environment that re-creates the pressure differential between the tissue interstitial pressure and the outflow capillary and venular pressure

Methodology Applied
Scientific EffectPressure differential: Pressure Gradient

Data Source

PatentUS7476541B1Bioreactor system and method for the production and collection of blood cells from engineered bone marrow tissue
Publication Date: 2009.01.13 DUTRA TIMOTHY F
  • US7476541B1 patent drawing
  • US7476541B1 patent drawing
  • US7476541B1 patent drawing

AI summary

Methods and apparatus for a bioreactor system for growing cells are provided. The bioreactor system includes a reaction chamber for cultivating harvested tissue in a culture medium, and a hydrodynamic apparatus connected to the reaction chamber that generates a cyclic negative pressure differential in the bioreactor. Additionally, the apparatus includes a collection enclosure for collecting cells produced by tissue in the reaction chamber. Also encompassed are embodiments for harvesting and preparing cells and tissue sections, combining the cells and the tissue sections in a culture medium to cultivate tissue, maintaining the tissue under conditions that permit production of cell products, applying cyclic negative pressure to the culture over a period of time, and collecting cell products discharged. Further disclosed are embodiments for placing harvested tissue and cells in a diffusion chamber, creating an oscillating negative pressure differential in the bioreactor over a period of time, and collecting the cell products.