Freeze Dryers: It's All About Temperature, Pressure, and Time

Freeze-drying, or lyophilization, is a long established process in the food, biotechnology, pharmaceutical, and diagnostic industries that involves the removal of water or another solvent from a frozen product by means of sublimation. This process is commonly used for improving product stability, for long-term preservation, for product purification, and for sample preparation.

By Trevor Henderson


While the immediate benefit of freeze drying is obvious—the ability to store samples at ambient temperatures—freeze-drying also may afford long-term savings by eliminating the need for costly cold storage.

The process of freeze-drying relies on the balance of only three controllable variables: temperature, pressure, and time. Although the process may seem straightforward, freeze-drying can often be problematic. Having an intimate understanding of the physical and chemical properties of the samples you are working with is essential to selecting a process and equipment best suited to your needs.

Knowing your sample

Controlling the freeze-drying process is dependent on two factors: the presence of a deep vacuum and a temperature differential of 15 to 20 degrees between the sample’s eutectic temperature (freezing point) and the temperature of the collector. Choosing a freeze dryer that meets the demands of your application can be a daunting task and requires careful consideration of the samples to be prepared. Choose a system that is too small and you will overload your collector; if your system doesn’t reach the correct temperature or has insufficient vacuum, you will risk sample melt back.

For many biological samples, including urea, blood plasma, serum, and vaccinia, a standard freeze-drying system with a refrigeration system that reaches -50°C will be sufficient. In the case of HPLC samples where the freezing point of acetonitrile is much lower (approximately -42°C), however, you will require a cascade-type collector. Cascade systems have dual condensers that can reach -84°C and would be a suitable choice for these samples.

Switching to methanol

Many labs are looking at methanol as an alternative to acetonitrile, due to its general availability and affordability. However, methanol has a much lower freezing point of -97.6°C, making lyophilization difficult even when it is diluted. In response to this demand, some manufacturers are offering ultra-low temperature freeze-dry systems. Labconco’s FreeZone systems, for example, are able to achieve collector temperatures as low as -105°C, making lyophilization of dilute methanol, ethanol, and acetonitrile possible.

A matter of timing

The most common question concerning freeze-drying is likely, “How long will it take?” The answer, however, is not so direct. The time required to freeze-dry a sample is dependent on a number of factors, including sample volume, thickness, and surface area; the eutectic point and solute concentration of the sample; and the temperature of the collector and the maximum vacuum obtained. In general, samples with a large surface area will freeze-dry faster than those that are thick or dense. Additionally, thick samples require moisture to pass through the layer of dried material, increasing the chance that the sample will thaw and “collapse.” Depending on your sample, freeze-drying can be a lengthy process lasting from hours to weeks. While freeze-drying provides superior drying capacity, if time is of the essence, you may consider a vacuum concentrator or evaporator for your application.

Finally, if you are shopping for a freeze-drying system, remember to budget for a rotary vane vacuum pump with vacuum deep enough to pull down to 2 x 103 mBar, as well as any glassware or adapters that may be required.

For additional resounces on freeze dryers, including useful articles and a list of manufacturers, visit 


Categories: Product Focus

Published In

Navigating The Post-Sequestration Landscape Magazine Issue Cover
Navigating The Post-Sequestration Landscape

Published: September 11, 2014

Cover Story

Navigating the Post-Sequestration Landscape

Job satisfaction and morale among researchers relying on government grants were body slammed by the sequestration—at least $1.3 trillion in across-the-board funding cuts were mandated by the 2011 Budget Control Act for 2013 through 2021.

Featured Articles

Cell Culture Reagents and Applications: Focus on 3D Cultures

Geoffrey Bartholomeusz, PhD, associate professor in the Department of Experimental Therapeutics and director of the siRNA Core Facility at the University of Texas MD Anderson Cancer Center, talks to contributing editor Tanuja Koppal, PhD, about why there is a growing interest in replacing some 2D cell culture applications with 3D cell cultures. He talks about where and why he uses 3D-based cell cultures in his lab and what lab managers should take into consideration before making the investment in this innovative technology.

Perspective On: A Clinical Research Lab

One of the major benefits of working in the sciences is the ability to have a positive impact on the world through research or the development of new products. That’s certainly the case with working at Redbiotec AG, a biotechnology company located at the Bio-Technopark in Schlieren, near Zürich, Switzerland.
We have updated our Privacy Policy to make it clearer how we use your personal data.
Please read our Cookie Policy to learn how we use cookies to provide you with a better experience.