In Vitro Cell Culture Model Using Shear Stress

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Solution Overview

Problem

Conventional in vitro models of pathological or physiological conditions require elevated concentrations of factors and often fail to accurately mimic in vivo responses, necessitating higher drug concentrations to induce desired effects.

Innovation Solution

The method involves applying shear force to cultured cells using a flow device, mimicking in vivo conditions by using culture media with factor concentrations within the in vivo range, allowing for the testing of drugs or compounds at physiologically relevant concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If conventional static tissue culture is used, then cell culture is simple to maintain, but factor concentrations must be elevated significantly above in vivo levels

Engineering Contradiction:
Improveease of cell culture maintenanceVSAvoidfactor concentration
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent applies dynamic fluid flow through the cell culture system to simulate physiological shear stress conditions. This dynamic approach replaces static culture with controlled flow conditions that mimic in vivo environments, allowing cells to respond to physiological factor concentrations rather than requiring elevated static concentrations.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent uses hydraulic flow systems to deliver culture media with physiological factor concentrations through channels over cell monolayers. This hydraulic approach enables the application of controlled shear stress while maintaining factor concentrations within in vivo ranges, resolving the contradiction between ease of operation and factor concentration requirements.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Ease of operation

If conventional static monocultures are used, then the system is simple to operate, but drug responses do not match in vivo responses at physiologic concentrations

Engineering Contradiction:
Improveease of system operationVSAvoidpredictive validity of drug response
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent implements dynamic flow conditions that replicate physiological shear stress, which is essential for accurate drug response prediction. This dynamic environment enables cells to exhibit in vivo-like responses to drugs at physiologic concentrations, significantly improving predictive validity compared to static systems.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the physical parameters of the culture system by introducing controlled fluid flow and shear stress. This parameter change transforms the culture environment from static to dynamic, enabling cells to respond to drugs in a manner that accurately reflects in vivo physiology at physiologic drug concentrations.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If elevated factor concentrations are used in static culture, then cell maintenance is achievable, but the system complexity increases to achieve physiologic responses

Engineering Contradiction:
Improvecell culture stabilityVSAvoidsystem complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent uses a relatively simple hydraulic flow system to achieve physiologic cell responses without requiring elevated factor concentrations. The flow device creates controlled shear stress that stabilizes cell composition and promotes physiologic responses, reducing the need for complex high-concentration factor regimens.

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The patent changes the physical state of the culture system from static to flowing, which fundamentally alters cell behavior and response characteristics. This parameter change enables stable cell maintenance under physiologic factor concentrations, achieving both stability and reduced system complexity compared to elevated concentration approaches.

Inventive Principle:
Principle #35Parameter changes

4Device complexity

If static culture conditions are used, then the setup is simple, but much higher drug concentrations are required to induce in vivo responses

Engineering Contradiction:
Improveculture system simplicityVSAvoiddrug concentration
Core Design Contradiction:
Device complexityVSQuantity of substance

Solution Approach 1:

The patent introduces dynamic flow conditions with controlled shear stress to simulate physiological environments. This dynamic approach enables cells to respond to drugs at physiologic concentrations rather than requiring elevated doses, significantly reducing the drug concentrations needed while maintaining relatively simple culture system design.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent employs a hydraulic flow system that applies physiological shear stress to cell monolayers. This relatively simple hydraulic setup enables cells to exhibit in vivo-like responses to drugs at physiologic concentrations, avoiding the need for complex high-dose drug regimens while maintaining system simplicity.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 effectively mimics in vivo conditions, enabling accurate testing of drug effects at concentrations that mirror in vivo scenarios, thereby improving the predictive validity of in vitro assays.

Implementation Method 1

applying a shear force upon the at least one plated cell type. The shear force results from flow of the culture media induced by a flow device

Methodology Applied
Scientific EffectShear force: Shear Stress

Data Source

PatentUS10514374B2In vitro model for pathological or physiologic conditions
Publication Date: 2019.12.24 HEMOSHEAR LLC
  • US10514374B2 patent drawing
  • US10514374B2 patent drawing
  • US10514374B2 patent drawing

AI summary

The present invention generally relates to in vitro methods for mimicking in vivo pathological or physiologic conditions. The methods comprise applying shear forces to a cell type or cell type plated on a surface within a cell culture container. Methods for testing drugs or compounds in such systems are also described.