Benefits of Using a Closed System for High-Density Cell Culture

Understanding the benefits of using a closed system for high-density cell culture could help your lab make the switch from initial research to scaling up cell growth for cell product harvesting. In addition to the complete systems available as ready-made solutions, prepackaged accessory options such as aseptic transfer caps help customize culture setups for a broad variety of applications and requirements.

What Is a Closed System?

closed system or closed loop system for cell culture enables an in vitro growth environment that minimizes or avoids exposing cells to potential contamination. Since most of this risk comes from liquid transfers, a closed system is equipped with access ports for adding growth media, removing waste, and performing other similar liquid transfers. Sterile connectors and other specialized ports that are integrated into tubing transfer solutions allow you to complete fluid exchange and harvest cells safely outside the biosafety cabinet while avoiding contamination.

What Are the Benefits of Using a Closed System?

Why switch to a closed system if an open system is working well? Although much of cell culture for research and development takes place using the more flexible open system approach, there comes a point in scaling up when this is no longer efficient. Benefits of using a closed system for high-density cell culture include:

Reduced Contamination Risk and Improved Safety

Using a closed system reduces the risk of contamination, which would otherwise compromise experimental results and negatively impact biological product quality. In addition, closed systems improve the biosafety of handling potentially hazardous organisms by blocking their release into the environment, thus protecting laboratory staff from exposure to biohazardous material and other potential pathogens.

Promote Consistency and GMP

A closed system promotes product consistency by maintaining a controlled cell culture environment that provides consistent cell growth conditions. Reducing the potential for human error and environmental variability can result in more reproducible outcomes and consistent product quality.

Configurable + Pre-assembled = Convenient Time Savings

Some closed systems are available as self-assembled components, such as various aseptic transfer caps and tubing sets available for specific cell culture vessels, and/or as fully pre-assembled closed systems, as seen in Corning closed system solutions. These ready-made systems can take less time to set up and preassembly further reduces the risk of compromising sterility during assembly. Examples range from complete cell growth systems to culture vessels such as Erlenmeyer flasks and roller bottles. The closed-system culture vessels come with all ports and tubing firmly attached for immediate use and connection. To complete the range, closed system-compatible reagent bottles make growth media and other solution transfers simple.

With closed system solutions, it's possible to manifold units and run routine liquid handling tasks for multiple vessels together instead of one by one. Corning also offers custom closed system solutions to meet specific cell culture needs using qualified components and tubing, aseptic transfer caps, and other single-use items configured to address your process requirements.

What Types of Closed Systems Are Available?

Closed systems can be as simple as growth vessels paired with aseptic transfer caps, featuring liquid transfer and venting ports that attach to cell growth vessels. These allow aseptic connection for liquid handling steps. More complex systems range from multilayered stacked growth platforms to benchtop or larger bioreactor systems for high-density cell production.

Corning CellSTACK® Culture Vessels

Corning CellSTACK Culture vessels have a versatile and expansive culture surface in a compact footprint. Available in 1-, 2-, 5-, 10-, and 40-layer stacked vessels, CellSTACK vessels can be manifolded for simplified liquid handling. A variety of aseptic transfer caps with tubing are available to replace the standard open system caps to enable means liquid handling and manipulation outside a biosafety cabinet.

Corning HYPERStack®

Corning HYPERStack Cell Culture Vessels are closed-system vessels that feature Corning High Yield PERformance technology, which incorporates a gas-permeable film to enable high-density cell culture with efficient gas exchange in a fixed medium volume. Available as 12- and 36-layer vessels, HYPERStack vessels provide up to 5X the growth surface area of a traditional stacked vessel in a comparable footprint. Preconfigured with liquid handling tubing and vent filters, HYPERStack vessels can be easily integrated into closed system setups for modular production.

Corning CellCube® Cell Culture System

The Corning CellCube Cell Culture System uses a compact, perfusion-based approach to scaling up adherent cell culture. CellCube modules, ranging in cell growth surface area from 8,500 to 85,000 cm2, feature multiple polystyrene plates separated by thin spaces to allow continuous media flow. Attached to a peristaltic pump, conditioned media circulation through the system provides effective nutrient and gas delivery to cells. Closed system CellCube modules are available preassembled with AseptiQuik® connectors and aseptic circulation loops for automated liquid handling.

Corning Ascent® Fixed Bed Reactor

The Corning Ascent Fixed Bed Reactor system is a complete closed system comprised of a controller, media conditioning vessel and fixed bed bioreactor. The novel bioreactor substrate of stacked woven PET disks promotes uniform media flow, cell adhesion, and growth while enabling high cell yield and viable cell harvest. The Process Development scale system offers bioreactors of 1, 2.5, and 5 m2. A Pilot version of the Ascent FBR system in development will offer up to 100 m2 of cell growth surface area.

How Do You Switch to a Closed System?

Switching to a closed system might require some adjustment and training from a qualified field scientist. One way to facilitate the switch and familiarize yourself with closed system solutions is to use scalable, convertible systems during the research and development phase. For example, Corning CellSTACK vessels are designed as an open system, but you can easily switch to a closed system using Corning aseptic transfer caps. Using a 2-layer CellSTACK vessel for initial studies makes it easier to scale up to 5- or 10-layer versions of the familiar growth vessel as a closed system.

Watch this video for a demonstration of different configurations of closed system CellSTACK vessels in the lab.