Spherical Cell Carriers with Relief Features Prevent Stacking

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Solution Overview

Problem

Conventional cell culture carriers face issues with clumping and sticking, which affect cell growth and nutrient transport, especially in bioreactors, limiting scalability and efficiency in adherent cell culture processes.

Innovation Solution

Development of cell carriers with relief features that minimize stacking and sticking, featuring dimensions and structures such as ridges, posts, and domed protrusions, which reduce interaction between carriers and reactor surfaces, facilitating uninterrupted cell expansion and release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Area of stationary object

If conventional microcarrier beads or planar carriers are used in bioreactors, then cell attachment surface area is increased, but carriers are prone to stacking and clumping which affects cell growth and nutrient transport

Engineering Contradiction:
Improvecell attachment surface areaVSAvoidcarrier stability
Core Design Contradiction:
Area of stationary objectVSReliability

Solution Approach 1:

The patent applies spherical curvature to the microcarrier design, creating carriers with a diameter of 0.5-2.0 mm that maintain a consistent spherical shape. This spherical geometry prevents stacking and clumping by ensuring uniform distribution in the bioreactor, while the curved surface provides adequate attachment area for cells. The spherical form eliminates flat surfaces that would otherwise cause carriers to stack against each other or against reactor walls.

Inventive Principle:
Principle #14Spheroidality (Curvature)

2Productivity

If planar carriers are used in bioreactors with intermittent agitation, then cell culture scale-up is enabled, but carriers are prone to stacking and clumping

Engineering Contradiction:
Improvecell culture scale-up capabilityVSAvoidcarrier structure
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The spherical geometry simplifies the carrier structure by eliminating complex planar configurations while enabling effective scale-up. The uniform spherical shape ensures consistent hydrodynamic behavior during intermittent agitation, preventing stacking without requiring complex structural features. This simple yet effective design allows straightforward scaling from small to large bioreactors.

Inventive Principle:
Principle #14Spheroidality (Curvature)

3Quantity of substance

If conventional carriers are used in bioreactors, then cell expansion is possible, but carriers stick to reactor walls and other surfaces

Engineering Contradiction:
Improvecell expansion capacityVSAvoidcarrier handling
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent employs density matching between the microcarrier material and the culture medium, creating a neutral buoyancy condition where carriers neither float nor sink. This counterbalances gravitational forces that would otherwise cause carriers to settle and stick to reactor walls. The carriers remain suspended in the medium, facilitating easy handling and uniform cell expansion throughout the bioreactor volume.

Inventive Principle:
Principle #8Anti-weight (Counterweight)

Data Source

PatentUS9453196B2Cell carrier, methods of making and use
Publication Date: 2016.09.27 GLOBAL LIFE SCIENCES SOLUTIONS USA LLC
  • US9453196B2 patent drawing
  • US9453196B2 patent drawing
  • US9453196B2 patent drawing

AI summary

A method of culturing adherent cells is provided, wherein the method comprises providing a carrier for growing the cells, comprising one or more surfaces; and one or more relief features/indentations are present on one or more of the surfaces, wherein the carrier has a length at least about 0.2 mm, a width at least about 0.2 mm, and a height in a range from about 0.012 mm to 0.5 mm; and wherein each of the relief features/indentations has a height above the surfaces in a range from about 2 to 200 μm, and width in a range from about 20 to 200 μm; seeding the cells on the carriers; and growing the cells on the carrier.