Tensegrity Force Application for CHO Cell Antibody Production

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Mammalian cell culture processes, such as those using Chinese Hamster Ovary (CHO) cells for producing recombinant proteins, face challenges including compressed product development timelines, capacity shortages, and limitations on proliferation and productivity.

Innovation Solution

Applying tensegrity forces, such as mechanical stress, shear stress, and pressure-induced stress, to mammalian cells like CHO cells to increase recombinant antibody production, using methods like magnetic twisting cytometry and biomechanical culture systems to modulate cytoskeletal structure and gene expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional cell culture processes are used, then current production levels are maintained, but productivity and proliferation limitations prevent further increase

Engineering Contradiction:
Improveantibody production levelVSAvoidcell proliferation limitation
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies mechanical stress parameters (tensegrity forces) to change the physical state of cells, triggering mechanotransduction pathways that increase antibody production. This resolves the contradiction by changing physical parameters rather than relying on conventional culture conditions that hit proliferation limits.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces conventional biochemical culture optimization with a mechanical stimulation approach. By applying controlled mechanical stress through tensegrity principles, the system achieves increased productivity without being constrained by traditional proliferation limitations.

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

2Productivity

If mechanical stress is applied to increase antibody production, then productivity increases, but cell viability may be compromised

Engineering Contradiction:
Improveantibody productionVSAvoidcell damage from stress
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies partial mechanical stress - enough to trigger mechanotransduction and increase antibody production, but controlled to remain below thresholds that would cause cell damage. This resolves the contradiction by finding the optimal partial application of stress.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The system monitors cell response to mechanical stress and adjusts application parameters accordingly, using feedback to maintain productivity enhancement while preventing cell damage. This ensures the stress remains in the beneficial range without crossing into harmful territory.

Inventive Principle:
Principle #23Feedback

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

Enhances antibody production levels by effectively transducing stress into cellular mechanisms, increasing the viability and productivity of cells, and allowing for scalable production in bioreactors.

Implementation Method 1

shear stress (torque) can be applied to the surface of a cell using membrane-bound ferromagnetic beads coated with antibodies that can adhere to the cytoskeleton of the cells. The beads can be magnetized in one direction by applying a weaker twisting magnetic field.

Methodology Applied
Scientific EffectMagnetic twisting: Magnetism

Implementation Method 2

pressure induced stress, for example, pressure induced by sound waves

Methodology Applied
Scientific EffectPressure induced by sound waves: Ultrasound

Data Source

PatentEP2454373B1Enhancement of cellular production through mechanotransduction
Publication Date: 2014.11.19 ABBVIE INC
  • EP2454373B1 patent drawingFigure 1

AI summary

Disclosed herein are methods of modulating protein production via the application of tensegrity forces on cells and cell cultures. The methods of the invention increase production of protein from cells and cell culture. The tensegrity forces can be stress that is applied to the cells, and can include one or more of the following; mechanical stress, shear stress, stretch effects, and pressure induced stress.