Freeze dryers, also known as lyophilizers, are complex instruments. Freeze drying involves multiple stages, from sublimation to desorption, and each step requires precise control. Regular maintenance must be performed to ensure the effective and efficient functioning of freeze-drying equipment, and specific cleaning tasks should be incorporated into Standard Operating Procedure (SOP). With the proper knowledge and approach, maintaining a freeze dryer doesn’t have to be daunting, so don’t lose your cool. Keep calm and carry on reading!

Throughout my career working in laboratories, the longer I spent with certain pieces of equipment, the more in tune I got with them. Things such as the hum of a pump become so recognizable that when the pitch or timbre changes, you notice – and it is likely that something has worn or some maintenance is required. With the proper preventative maintenance, however, such issues should not occur, and you can rest assured that your equipment is functioning as it should. Maintenance is also essential when reproducibility is a consideration, as worn or out-of-spec parts will hinder the accuracy of results.

With the proper preventative maintenance, you can rest assured that your equipment is functioning as it should.

I have spoken before about maintenance concerning vacuum pumps , heating baths , and glassware . In this blog, though, I would like to tackle one of the more complex pieces of laboratory equipment, the freeze dryer. I recently spoke about how to use spray drying to create advanced batteries and inhalable drugs . Neither of these precision tasks could be achieved without well-maintained equipment. Lyophilization is a complex process that requires precision at every step. The instruments must maintain and sustain very low temperatures and pressures to facilitate sublimation. To achieve this, vacuum pumps, gauges, regulation valves, various seals, the refrigeration system, and control systems all need to work in unison, and if any fail, then further problems can occur. So, without further ado, here’s how to ensure your freeze-drying equipment’s longevity and proper functioning.

Instrument Choice
If you choose the wrong instrument for the task, then no amount of maintenance will help. Even the world’s best-maintained penny-farthing bicycle will not compete in the Tour de France! Regarding freeze dryers , many systems are available with varying temperatures, capabilities, and configurations. You need to know the amount of vapor from solvents the instrument will have to handle and what types of samples will be freeze-dried. If the collector is too small, the unit cannot reach the correct temperature at the sample loading/attachment; it will be unable to collect the sample vapor. In the first hours after the sample is attached, the sublimation is very strong, requiring the unit to maintain a suitable condenser temperature. Furthermore, the small size brings about the misery of constant defrosting due to limited ice capacity. There is also the choice of the pump to consider; a robust pump will reach vacuum quickly and reliably maintain pressure. You must know whether your samples are acid, water, organic solvent, or a mixture. Most water-based samples can be used with a -55 °C freeze-dryer. Samples containing some fraction of solvents may benefit from a -55 °C freeze-dryer with a dry pump that doesn’t require oil. The condenser capacity determines how many kg of ice/ liters of water can be contained on the coil. It is essential not to overload the ice condenser as it will hinder the sublimation process. If ice accumulates on the condenser, the collection becomes less efficient until no more ice can be trapped. Some maintenance can be avoided with modern instruments that offer continuous sublimation , thanks to two alternately working condensers that are automatically cleaned.

Overloading the ice condenser will hinder the sublimation process. If ice accumulates on the condenser, the collection becomes less efficient until no more ice can be trapped.

Sample Prep
Freeze-drying samples properly requires a difference in temperature between the sample and the condenser of at least 15 °C – 20 °C. The sample will bypass the collector and enter the vacuum pump if it is not cold enough, leading to possible damage and extra maintenance. Some organic solvents have a freezing point so low that no freeze dryer will be able to accommodate them without some sample preparation. In such cases, the sample can be diluted, or evaporated in a rotary evaporator before freeze-drying.

Sensor Instrumentation System
Freeze dryers include temperature and pressure sensors that should be checked regularly and recalibrated when required. In systems with a Pirani gauge and a capacitance manometer, you can check these vacuum sensors by running the instrument empty and dry (Pirani gauges read high in the presence of water vapor) with a set pointer at 0 mbar. Both gauges should be in agreement when a relatively low pressure has stabilized. If the sensors differ, then one of the probes likely needs recalibrating.

Vacuum System and Drying Chamber
Vacuum pumps are either:

– Wet (oil-lubricated): Two-stage rotary vane pumps.
– Dry (oil-free): Scroll pumps.
– Hybrid.

Oil-Lubricated Pumps
These inexpensive pumps can reach very low vacuum, though it is essential to keep an eye on the quality of the oil and perform changes regularly – ideally every 2000 working hours, but potentially more if a solvent other than water is used. A visual inspection is recommended before and after each freeze-drying cycle. If it has darkened, it’s time for a change.

It is good practice to open the gas ballast of these pumps after a run for 10-15 minutes before switching off. This enables the solvent vapors that have not condensed to evacuate. Don’t forget to close the gas ballast afterward to avoid oil being carried to the exhaust.

Oil-Free Pumps
Scroll pumps are recommended for aqueous and solvent samples. Special care must be taken when acids are used since the scrolls are metallic. These pumps are more expensive but require less maintenance. No oil change is required; however, the scrolls must be replaced every 40,000 working hours to ensure optimal vacuum. Opening the gas ballast for half an hour to one hour daily is mandatory.

Hybrid Pumps
These pumps are ideal for corrosive and volatile substances and combine rotary vane and diaphragm pumps. The oil of the rotary vane pump is kept under negative pressure by a diaphragm pump. This reduces the vapors passing through and condensing in the oil. Oil can last up to 10 times longer, reducing the amount of maintenance required.

O-Rings and Gaskets
These must be visually inspected for cleanliness, dryness, or cracks and can be cleaned from dust with a damp cloth containing mild detergent or water. They can be lubricated with a small amount of high-vacuum grease if needed. Damaged seals should be replaced immediately.

Acrylic Parts, Manifold Valves, Glassware.
Visually inspect each of these to ensure cleanliness and watch out for cracks or etching. Pay extra attention to acrylic parts if organic or acidic solvents are used. Manifold valves will require regular cleaning, and beware that even a tiny scratch can cause glassware to implode when exposed to a high vacuum.

Perform Regular Vacuum and Leak Tests.
Perform a vacuum test at the ultimate vacuum of 0 mbar in a clean and dry system with the condenser on. Ensure it reaches the technical specifications of the vacuum pump that may require servicing. See my detailed blog on performing a leak test on a rotary evaporator to learn more as the same principles apply.

Drying Chamber
After each run, the drying chamber must be cleaned, paying attention to the removal of spilled product, broken glass, and vial stoppers. Clean all stainless steel and acrylic surfaces, drain all solvents, and dispose of them properly. Any acids used should be neutralized to protect the instrument.

By following the instructions above, your freeze dryer will work optimally each time it is used. As with all technical equipment, be sure to read and consult the manual and consult your service engineer to determine the correct interval for maintenance. You can also purchase tailored maintenance packages or training sessions with certified experts to ensure the longevity of your valued equipment. I hope this information has been useful and helps you keep your cool if something goes wrong.

Till next time,