Anyone who needs to freeze-dry samples often knows how long it can take. Regardless of what freeze-drying methods you use, each stage in the process is vital to ensure the longevity and usability of your samples. The process can take days, depending on the sample and conditions in your lab, which can slow down all the associated operations in your workflow.
Knowing how to speed up your freeze-drying process without risking the integrity of your samples can save you valuable hours. Luckily, there are some tricks you can use to achieve this seemingly difficult task — without too much difficulty.
What Is Freeze-Drying?
Freeze-drying is a process used to preserve samples by removing moisture via sublimation. In other words, you change the phase directly from solid to gas. A freeze-dryer — or lyophilizer — is the equipment that makes this process possible.
The process involves lowering the temperature of a sample to below freezing and then applying a high-pressure vacuum to extract water and other solvents in the form of vapor. If you freeze-dry something, you can preserve it for longer, which is essential in many settings, including food and beverage, archaeology, medicine and science.
In many laboratories, one of the challenges is to use a preservation method that doesn't cause physical or chemical changes to the sample. Freeze-drying can preserve sensitive, unstable or heat-sensitive materials without changing their structure, making the process vital in many laboratory settings for the following applications:
- Vaccines and antibodies
- Blood plasma
- Pathological samples and cultures
- Viruses and bacteria
- Protein and enzymes
- Active pharmaceutical ingredients
The 3 Stages of Freeze-Drying
The freeze-drying process requires samples to go through three distinct stages, including the following:
- Pre-freezing: In this stage, you prepare your samples for sublimation by cooling them past the solvent's melting point. This vital element of the lyophilization process ensures that the sample is entirely frozen and undamaged during primary drying.
- Sublimation: The second stage of the process — also known as primary drying — involves powering on a vacuum pump, which simultaneously lowers the sample's chamber pressure and boiling point. Then, the sample is heated via either a heat source built into the chamber or transfer from the environment, which sublimates the solvent.
- Desorption: This secondary drying process removes all moisture from the sample, as primary drying may still leave residual moisture.
How to Speed Up Your Freeze-Drying Process
The lyophilization process is time-intensive. Without proper management and methods to reduce the time without impeding the process, you could experience delays and interruptions in your workflow. Knowing how to operate a freeze-dryer is one thing, but there are some tips and tricks you can use to speed up the process.
1. Watch Your Process Parameters
With a few process changes, you can freeze-dry faster. Firstly, you can increase the surface area of your frozen sample by using larger vials and reducing the fill volume. Next, see if you can find a way to increase the energy supply for the sublimation stage by using shelves you can heat at elevated temperatures. Ensure you increase the pressure in the drying table as much as the sample temperature allows.
Spreading out the sample and pre-freezing in a thin layer covering your flask is known as shell freezing — a popular choice for manifold freeze-drying. You can purchase commercial shell freezers, but if this isn't an option, freeze your samples at a slant to increase the surface area as much as possible.
2. Reduce Hands-On Time
Although this may not speed up the process, reducing hands-on time at the instrument frees you up to complete other tasks while the lyophilization continues. Look at systems with remote control options and features like remote process start and data and method handling.
3. Maintain Consistent Ice Condenser Temperatures
Consistent ice condenser temperatures make freeze-drying quicker and more reliable. The more powerful your cooling systems, the shorter your setup time, and with the right equipment, you can reduce it to as little as five minutes. Maintain a 59-68 degrees Fahrenheit difference between the ice condenser and the frozen sample.
4. Know Your Eutectic Points
Eutectic temperature is the temperature at which samples only exist in the solid phase. Your samples must stay frozen at every stage of freeze-drying, and if your frozen sample reaches a higher temperature than the eutectic temperature, it starts to melt.
The more heat you add in the primary drying phase, the faster your process becomes, but your sample must stay below its eutectic point. Knowing the eutectic temperature allows you to add maximum heat without risking your sample.
If you still need to establish the eutectic temperature of a sample, add heat slowly and monitor until you can determine the maximum heat you can add to a sample.
5. Set Your Vacuum Level
You must provide your sample with energy in the form of heat for it to sublimate. Molecules around the sample help with heat transfer — if there aren't any, heat transfer is challenging.
The fastest evaporation rates require a vacuum level of .200 bar. Lower vacuum levels don't provide enough molecules for an effective heat transfer. Levels above .200 bar have too many molecules present, and this density slows down sublimation rates. Ensure you set your vacuum level correctly before you start freeze-drying.
6. Use Heated Shelves
If you have a shelf freeze-dryer, heatable shelves are an excellent accessory for adding extra heat to your samples. You can automatically control and adjust your shelf temperatures depending on your system. If you want to look for a freeze-dryer, look for heatable shelves with precise heat input control — the less guesswork you have to do, the faster your process.
7. Monitor Your Times
Primary drying sublimates all the free molecules so secondary drying can begin. As most of the water has already been sublimated, you can raise the sample temperature above the eutectic temperature without worrying about melting.
Knowing when the sublimation process is complete can be challenging, and if you end it early, the sample can melt back. As a result, it's common practice to be cautious and freeze-dry for longer than needed. If you know when the exact endpoint is, it can speed up the process significantly.
Some freeze-dryers have built-in endpoint detection, but if you don't have this feature, remember that sublimation no longer occurs when the sample and shelf temperatures are equal.
8. Choose the Right Freeze-Dryer
Lyophilization can only occur if you add energy in the form of heat, and as we discussed, the more energy you can transfer to the sample within the limits of the eutectic point, the faster your process. When buying a freeze-dryer, choose one that allows you to add heat to your samples.
Tray dryers add heat through heated trays. Flask and manifold setups, however, rely on heat from the ambient temperature in the room, which should be between 59-68 degrees Fahrenheit. Remember that temperature changes affect lyophilization times if you choose a manifold freeze-dryer.
Find the Lab Equipment You Need With New Life Scientific
Streamlining your workflow is a consistent goal for any laboratory, and the right equipment can help you in this endeavor. New Life Scientific can help you find the best equipment for your budget without unnecessary risk.
Our technicians test and repair our collection of used lab equipment before you buy, and we pride ourselves on being honest about what you're buying and what you can expect. With a 120-day warranty, you can trust that your equipment works as it should, and you can always reach out to our friendly and knowledgeable staff if you have questions or concerns.