Your Guide to the ATF Bioreactor Sterilization Cycle

Amit Gupta
Written by: Amit Gupta

MS Mechanical Engineering, Vice President of Engineering

The ATF Bioreactor Cycle is designed to permit the sterilization of hollow fiber filters while housed in bioreactors such as those made by Repligen and Spectrum Labs. This cycle is a relatively new addition to the typical list of sterilization cycles normally found in laboratory autoclaves.

Below is an explanation of the ATF Bioreactor Sterilization Cycle and how it works.

What is the ATF Bioreactor Sterilization Cycle?

Alternating Tangential Flow (ATF) is a technology used in the perfusion culture of mammalian cells, proteins and antibodies.

ATF bioreactors use hollow fiber filters and have become increasingly popular in the production of secreted protein products from cell cultures held within the bioreactors. The filters allow for a steady stream of nutrients to the cell culture while simultaneously harvesting product secretions and removing waste products, effectively maintaining the culture at a highly productive steady state and achieving very high cell density. Products such as blood clotting factors, antibodies and enzymes can now be harvested at far more efficient rates and costs while using comparatively small-volume reactors.

These fibers have extremely small diameters (0.1-0.65 micrometers) and small aspect ratios. As such, rapid changes in either temperature or pressure can cause severe damage to the fibers thereby preventing proper operation. Because of the cost of these filters, particular attention should be given to the sterilization process in order to prevent damage. Cycles typically found on autoclaves such as gravity, liquid or pre-vacuum are generally not recommended by ATF filter manufacturers.

How the Process Works

The ATF Bioreactor Cycle incorporates a series of slow temperature ramps and hold times to allow pressure and temperature gradients to equalize across the filter. This helps prevent damage to the delicate fiber filter. This cycle, available on Consolidated autoclaves with X1™ control systems, uses existing load probe sensor technology combined with high precision steam control to ensure that multi-use ATF filters can be safely autoclaved to the users’ exact specifications.

Beyond software configurations, a steam sterilizer capable of running an ATF Bioreactor Cycle includes several hardware options. For example, these sterilizers are equipped with load probes for measuring temperatures at or near the surface of the bioreactor, steam flux electric solenoid valves for post-cycle temperature actuation, and loading carts and transfer carriages to easily transport the ATF filters in and around the sterilizer. A minimum chamber height of 36″ is recommended.

A sterilizer designed for use with ATF filters will also need to be equipped to handle clean steam. Clean steam is generated by boiling distilled or deionized water from a purified water source. Because of its purity, clean steam will aggressively degrade any autoclave constructed with brass, bronze or carbon steel plumbing, therefore all stainless-steel construction is required. You can find more information in our article, A Guide to Autoclave Steam Sources.

If you have questions about sterilizing bioreactors with ATF, or any other small-fiber sterilization application, please contact Consolidated Sterilizer Systems and our team of engineers will be happy to assist.

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