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15-Lyophilizers

Lyophilizers: A Complete Guide

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Lyophilizers: Introduction

Lyophilizers are sophisticated instruments that facilitate the process of lyophilization. Lyophilization or freeze-drying is a precise and costly technique used for the preservation of products, such as astronaut food, biopharmaceuticals, food products, and museum exhibition objects. 

Note that during lyophilization, the sample is dehydrated through sublimation without shrinkage or loss of structure.

Interestingly, the act of lyophilization is an ancient process practiced for thousands of years. The Incas, for instance, managed to tame the cold temperatures of the Andes and their high altitudes to produce freeze-dried food. 

Over the centuries, lyophilization became part of laboratory practices and industrial processes across the world. 

To provide an example, in 1890, the German pathologist Richard Altmann used a method to freeze-dry tissues, while in 1903, scientist Vansteenberghe dried the rabies virus under vacuum. 

On the other hand, in 1905, Benedict and Manning reported drying animal tissue via a chemical pump, while in 1906, the French physician Jacques Arsene dā€™Arsonval removed water at a low temperature. 

However, it was Leon Shackell who in 1909 recorded the use of sublimation for dry tissue and biological materials (via a vacuum chamber and an electrical pump), and inventors Henri Tival and William Elser who received the first patents for modern freeze-drying systems (in 1927 and 1934, respectively). 

Consequently, the process of lyophilization was popularized in the 1930s. In fact, the commercial applications of freeze-drying were enhanced by the work of Earl Flosdorf, who in 1933 freeze-dried blood serum and plasma for medical use. 

We should note that freeze-drying was invaluable during World War II for the transportation of blood plasma and penicillin.

Freeze-drying has evolved significantly over the years. Now lyophilization is an invaluable process in chemistry, medicine, research, cosmetics, astronautics, high-volume production, and food processing. 

Surprisingly, more than 400 freeze-dried products have been manufactured since the 1960s, with coffee being the most popular and in-demand freeze-dried product. 

When it comes to medical and research settings, lyophilizers are used to preserve food, vaccines, bacteria, and clotting factors; they can also apply to raw materials in drug manufacturing and sample preparation. 

Some of the most notable equipment manufacturers across the globe are Zirbus Technology, Harvest Right, and Labconco.

Buying a Lyophilizer: Factors to Consider

Lyophilizers are invaluable tools in lab settings used to increase the shelf life of vaccines and other pharmaceutical products; freeze dryers can also facilitate the transportation of biopharmaceuticals. 

Additionally, some medicines can be freeze-dried in order to be easily absorbed, while some proteins and antibodies are freeze-dried for stability. Given the wild applications of lyophilization, itā€™s no surprise thereā€™s a variety of lyophilizers experts can choose from. 

Whether itā€™s to set up a new laboratory or replace old equipment, there are three major factors to consider before purchasing a new unit:

Requirements: Before buying a freeze dryer, experts should refine their research and production goals. Both the sample size and type are crucial factors to consider. While benchtop models are ideal for small volumes, floor standing models are beneficial for large-scale applications. 

When it comes to sampling types, a difference of 15-20Ā°C is needed between the eutectic temperature of the sample and the collector chamber. 

While the majority of biological samples can be frozen by a standard system reaching -50Ā°C, some samples, such as High-Performance Liquid Chromatography/HPLC preparations in acetonitrile/CH3CN, will need a cascade-type collector reaching -84Ā°C to accommodate lower freezing points. 

An ultra-low temperature lyophilizer (of up to -105Ā°C), on the other hand, might be required to accommodate preparations with methanol (with a eutectic point of -97.6Ā°C). 

For acidic samples that can harm the stainless steel coils of a system, Polytetrafluoroethylene/PTFE coating is recommended, as well as a hybrid-type pump. Last but not least, the volume of liquid should be considered. 

While lyophilizers with a small capacity can accommodate tissue samples with small amounts of liquid, food products may hold higher amounts and require units with a bigger capacity. Note that collector capacities can vary from 2.5 to 18 liters, with different shelving and holders.

Specifications: As explained above, different research goals require different equipment. Capacity parameters, materials used, and design types are all factors to consider. Yet, we should note that all lyophilizers follow three vital processes to execute water removal: 

1) freezing to preserve the sampleā€™s physical form; 

2) sublimation drying that removes 95% of the water; 

3) secondary drying or desorption drying used to remove any remaining water molecules. 

Interestingly, after lyophilization, products contain 1-4% moisture and are nitrogen sealed for further use. Note that lyophilization differs from evaporation (the use of heat to eliminate moisture), and sublimation refers to the direct transition from a solid to a gaseous state.

Total costs: Lyophilization is an expensive process due to equipment costs, long processing times, and energy costs. Prices can vary according to the unitā€™s parameters (e.g., temperature range, capacity, type, and brand). 

Note that full-sized models can process multiple samples in a single cycle; some units may even have more than one condenser for almost continuous use. Control systems can also vary in complexity, with some allowing the programming of a whole freeze-drying recipe, which can also affect costs. 

Furthermore, drying accessories, which can be customized according to the research goals, should be considered. To test tubes and serum vials, for instance, flasks can be used, while for bulk samples, a tray dryer will be preferable. 

Additional equipment, such as glove boxes for toxic materials and accessories to stopper under vacuum, can increase the final price of a unit.

Types of Lyophilizers

Lyophilizers come in all shapes and sizes. Note that freeze dryers are often classified by the type of chamber: manifold benchtop units, shelf consoles, and combination models. Another classification offers four categories according to the specific research goals: 

1) lab freeze dryers: with a shelf area of 0.1 sq.m. to 1 sq.m.; used for simple removal, Phase 1 clinical trials, and scale-up production; 

2) production units: with a shelf area of 1 sq.m. to more than 40 sq.m.; employed for high-volume productions, as well as Phase 2 and Phase 3 trials; 

3) sterilizable lyophilizers: units that are used when sterilization between cycles is needed, which is done through pressurized steam or hydrogen peroxide; 

4) non-sterile freeze-dryers: units that are usually more affordable than sterilizable units. 

Interestingly, the presence of additional features, such as shelf style (bulk or stoppering), condenser location (internal or external), and material used (316L or 304L), are also utilized to classify lyophilizers.

Best Lyophilizers on the Market

Whether itā€™s for cultures and food processing or material stabilization and storage, thereā€™s a wide range of lyophilizers experts can choose from. 

As explained above, different research settings require different lyophilizers. Based on different parameters and user reviews, here are some advanced lyophilizers ideal for lab settings:

  1. Labconco 700201000 Free Zone Benchtop Freeze Dryer with Non-Coated Stainless Steel Coil, 2.5 L Capacity, -50 Degree C, North America Plug, 115V, 60 Hz, 14A

Labconco 700201000 Free Zone Benchtop Freeze Dryer with Non-Coated Stainless Steel Coil, 2.5 L Capacity, -50 Degree C, North America Plug, 115V, 60 Hz, 14A is a wonderful benchtop model with a small footprint. 

This 2.5-liter lyophilizer is made for light sample loads. The stainless steel collector coil can hold up to 2.5 liters of ice, and its refrigeration system can cool the collector to -50Ā° C (-58Ā° F). With its compact design and advanced features, this lyophilizer is ideal for small labs and limited floor space.

  1. Labconco 794801300 Free Zone Stoppering Tray Dryer with 6-Port Manifold and Isolation Valve, North America Plug, 115V, 60 Hz, 16A

Labconco 794801300 Free Zone Stoppering Tray Dryer with 6-Port Manifold and Isolation Valve, North America Plug, 115V, 60 Hz, 16A is a beautiful model with a white exterior and blue accents. 

This unit is ideal for moderate to large loads and allows the stoppering of vials or serum bottles under a vacuum. Note that the chamber pre-freezes samples and two LEDs show ā€œPower/Standbyā€ and ā€œIn Process.ā€ With a variety of features, this lyophilizer is ideal for various research settings.

  1. Lyovapor L-200 Pro Control Freeze Dryer with Combined Heated Shelf and stoppering top, Pfeiffer Duo 6 Pump with Advanced Vacuum Control

Lyovapor L-200 Pro Control Freeze Dryer with Combined Heated Shelf and stoppering top, Pfeiffer Duo 6 Pump with Advanced Vacuum Control is a compact unit with a user-friendly touch-screen. 

This freeze dryer allows fully automated processing, as well as data logging and chart recording in real-time. Note that the drying chamber enables stoppering under an inert atmosphere. With its rich settings, this model is ideal for high-quality freeze-drying.

  1. Labconco 711212010 Free Zone Console Freeze Dryer with PTFE-Coated Stainless Steel Coil, 12 L Capacity, -84 Degree C, North America Plug, 230V, 60 Hz, 9A

Labconco 711212010 Free Zone Console Freeze Dryer with PTFE-Coated Stainless Steel Coil, 12 L Capacity, -84 Degree C, North America Plug, 230V, 60 Hz, 9A is ideal for moderate to large samples or numerous small container batches. 

The unit has a front viewing window, as well as sufficient space for a vacuum pump (sold separately). Note that this lyophilizer can fit a full-size tray dryer and hold up to 12 liters of liquid. 

As this unit can cool materials down to -84Ā°C (-119Ā°F), it is suitable for low eutectic point samples, including acetonitrile. With different built-in options, Labconco 711212010 is ideal for numerous research settings.

  1. Labconco 701822115 Free Zone Console Freeze Dryer with Stoppering Tray Dryer and PTFE-Coated Stainless Steel Coil, Purge Valve, 18 Liter Capacity, -50 Degree C, Saudi Arabia Plug, 230V, 60 Hz, 9A

Labconco 701822115 Free Zone Console Freeze Dryer with Stoppering Tray Dryer and PTFE-Coated Stainless Steel Coil, Purge Valve, 18 Liter Capacity, -50 Degree C, Saudi Arabia Plug, 230V, 60 Hz, 9A is a great unit, which can be used for holding moderate to large loads and stoppering vials or serum bottles under vacuum. 

Note that its upright stainless steel collector coil is capable of holding 18 liters of ice before defrosting. Also, this console features a front viewing window and interior space for a vacuum pump (sold separately). Last but not least, the lyophilizer has a side-mounted USB port and rear-mounted Ethernet connection.

  1. CGOLDENWALL JK-FD-2 Freeze Drier Freeze drying machine (ordinary type)

CGOLDENWALL JK-FD-2 Freeze Drier Freeze drying machine (ordinary type) is a great desktop-type freeze dryer with a condensing temperature of -45 Ā°C and lyophilized time of around 24 hours (material thickness of 10mm). This unit can be used for drugs, biological products, chemicals, and food industries.

Lyophilizers | Maintenance

Given the fact that lyophilization is a costly process, taking care of equipment is essential. Always consult instruction manuals to ensure safe setup and accurate use. 

As freeze-drying is a precise process, users should account for numerous risks, such as excessive vapor, condenser overload, and insufficient refrigeration. Note that vendors recommend loading half of the unitā€™s listed capacity (e.g., three liters during a single run in a 6-liter unit). 

To ensure accurate use and long life, cleaning and maintenance are essential. Some recommended steps include cleaning collectors, neutralizing the unit from acids, and basic oil changes on the vacuum pumps. In the end, proper equipment can only guarantee properly freeze-dried products.

Lyophilizers: Conclusion

Lyophilizers are sophisticated instruments used for the preservation of a variety of products, such as vaccines, bacteria, proteins, enzyme hormones, antibiotics, blood plasma, and food. 

Note that during the process of lyophilization or freeze-drying, the sample is dehydrated by means of sublimation, without shrinkage or loss of structure. 

To be effective, lyophilizers are based on three major principles: freezing, sublimation, and secondary drying. Note that sublimation refers to the direct transition from a solid to a gaseous state.

Whether itā€™s for setting up a new lab or replacing equipment, choosing a lyophilizer can be tricky. While freeze dryers come in different shapes and sizes, users should consider three major aspects: requirements, specifications, and total costs. 

Interestingly, while benchtop models are ideal for small volumes, floor standing models are beneficial for large-scale applications. Note that prices can vary according to the unitā€™s parameters (e.g., temperature range, capacity, type, and brand). 

Purchasing additional accessories should also be considered. While freeze-drying has been known for thousands of years, technology has evolved significantly, making lyophilizers vital instruments in lab research and production settings.