Dynamic Stiffness Control in Cell Culture Substrates

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Solution Overview

Problem

Current cell culture substrates lack dynamic and reversible control of substrate elasticity, limiting the ability to induce different cell growth characteristics such as morphology, motility, and differentiation, as they are either static in stiffness or require physical stress during surface changes.

Innovation Solution

A cell culture apparatus with removable members of varying stiffness, allowing for dynamic and reversible control of substrate elasticity, enabling cells to be exposed to different stiffnesses simultaneously or over time without physical stress, using a containment layer that allows cells to adhere and sense the environment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If polymeric substrates with fixed stiffness formulations are used, then substrate stiffness can be tuned for specific cell studies, but the material properties are fixed and not dynamic, limiting temporal control

Engineering Contradiction:
Improvetemporal control of stiffnessVSAvoidsystem formulation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies UV-photomodulatable hydrogels that enable dynamic temporal control of substrate stiffness through light irradiation. The hydrogel formulation contains photomodulatable crosslinkers that can be activated or deactivated by UV light, allowing the stiffness to change from soft to stiff states on demand, transforming a static system into a dynamic one.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the physical-chemical parameters of the hydrogel system by incorporating photomodulatable crosslinkers and controlling UV irradiation conditions. This allows the stiffness parameter to be dynamically adjusted through parameter changes in the crosslinking density, enabling temporal control without requiring complex mechanical actuation systems.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If UV photomodulatable hydrogels are used to dynamically control stiffness, then temporal stiffness control is achieved, but the change in stiffness is not reversible spatially or temporally

Engineering Contradiction:
Improvereversibility of stiffness changeVSAvoidstiffness control reliability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs periodic UV irradiation cycles to achieve reversible stiffness changes. By alternating between UV irradiation (which stiffens the hydrogel through crosslinking) and dark periods (which allow relaxation and softening), the system creates a periodic action that enables reversible temporal control of stiffness, transforming the irreversible process into a reversible cycle.

Inventive Principle:
Principle #19Periodic action

3Ease of manufacture

If thin-film PDMS is directly spin coated or poured into molds, then thin-film fabrication is achieved, but the PDMS sticks to the underlying substrate and requires large peeling forces that may tear the film

Engineering Contradiction:
Improvethin-film fabrication easeVSAvoidfilm integrity during removal
Core Design Contradiction:
Ease of manufactureVSStrength

Solution Approach 1:

The patent introduces a release layer as an intermediary between the PDMS thin-film and the underlying substrate. This release layer acts as a mediator that prevents direct adhesion between the PDMS and substrate, allowing the thin-film to be easily removed without applying large peeling forces that would tear the film, thus solving the adhesion problem while maintaining film integrity.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of manufacture

If polyelectrolyte multilayer fabrication by successive spin coating is used, then bilayer polymeric substrates can be fabricated, but the individual layers cannot be separated from the bilayer structure

Engineering Contradiction:
Improvebilayer substrate fabricationVSAvoidlayer separability
Core Design Contradiction:
Ease of manufactureVSWeight of moving object

Solution Approach 1:

The patent segments the bilayer polymeric substrate into independently separable layers by incorporating a release layer between the layers. This segmentation allows the individual layers to be separated from the bilayer structure without damage, enabling independent manipulation of each layer while maintaining the ability to fabricate the complete bilayer substrate through successive spin coating.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS9976113B2Methods, apparatuses, and systems for cell and tissue culture
Publication Date: 2018.05.22 CARNEGIE MELLON UNIV
  • US9976113B2 patent drawing
  • US9976113B2 patent drawing
  • US9976113B2 patent drawing

AI summary

This invention provides an apparatus and method for culturing cells to probe the influence that the properties of a surface onto which the cells are bonded has on the properties of the cell.