A practical reference on secondary drying: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2025-08-21. Anything still debated is marked as such rather than presented as settled.
The low pressure used during drying allows water vapor to move from the ice surface to a cold condenser. Energy supplied as heat drives sublimation but must stay below the collapse temperature of the frozen matrix. If the product becomes too warm, the frozen structure may soften or melt, reducing pore formation and slowing drying. Formulations often include bulking agents, stabilizers, or buffers to support a rigid cake. The final moisture content depends on formulation, freezing rate, and the length of secondary drying.
Freeze-drying is distinct from simple evaporation and from spray drying. Evaporation removes water at temperatures above freezing, while spray drying rapidly dries droplets in a heated gas stream. Lyophilization avoids high temperatures, which can be useful for heat-sensitive materials such as proteins, vaccines, and some foods. The porous cake produced by sublimation dissolves or rehydrates more quickly than a dense dried mass. Not all materials tolerate freezing or the pH shifts that can occur as solutes concentrate during ice formation.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen to convert liquid water into ice. Next, the pressure is reduced below the triple point of water so that ice changes directly into vapor without passing through a liquid phase. This step is called primary drying. The result is a porous solid or cake that retains the original shape of the frozen solution.
After primary drying, secondary drying removes water that remains bound to the material. This stage raises the shelf temperature while maintaining low pressure, which encourages desorption of unfrozen water. Residual moisture can be reduced to a low percentage, improving stability for many products. The process parameters, including freezing rate, shelf temperature, and chamber pressure, influence the final pore structure and reconstitution behavior. Control of these variables helps prevent collapse or meltback during drying.
| Property | Value | Notes |
|---|---|---|
| Primary phase change | Sublimation | Ice changes directly to vapor under reduced pressure |
| Typical chamber pressure | 0.01–0.5 mbar (1–50 Pa) | Below the triple point of water; product-specific |
| Typical product temperature during primary drying | −40 °C to −10 °C | Kept below collapse temperature |
| Typical residual moisture | 0.5–3% w/w | Target range varies by formulation and use |
| Common synonyms | Freeze-drying; lyophilisation | Lyophilization is the US spelling |
Lyophilization, also called freeze-drying, is a dehydration process in which a solvent, usually water, is frozen and then removed by sublimation under reduced pressure. The method preserves heat-sensitive materials that would degrade in conventional drying. Large-scale use grew during the mid-twentieth century for blood plasma and antibiotics, and it later expanded to vaccines, enzymes, foods, and advanced materials. The process produces a dry, porous solid that usually reconstitutes rapidly. It is distinct from simple evaporation because the solvent bypasses the liquid phase during primary removal.
The process generally proceeds in three stages: freezing, primary drying, and secondary drying. During freezing, controlled cooling converts water into ice and may also crystallize or vitrify solutes. In primary drying, the pressure is lowered below the triple point, and heat is supplied so ice sublimes directly to vapor. Secondary drying removes water that remains bound to the solid matrix, yielding a low final water content. Product temperature must stay below the collapse or glass transition temperature to maintain structure. Cycle design therefore balances shelf temperature, chamber pressure, and time.
Freeze-drying is used for materials whose activity or structure depends on low temperature and low water content. Examples include certain biologics, diagnostic reagents, starter cultures, coffee, and porous inorganic precursors. The dried product forms a cake whose porosity aids rapid wetting and dissolution. Main drawbacks are high energy use, long cycle times, and sensitivity to formulation and equipment variation. Questions remain about how freezing rates and ice morphology affect batch uniformity, especially when moving from laboratory to production scale.
The process usually has three stages: freezing, primary drying, and secondary drying. Freezing sets the ice crystal structure and can determine pore size in the final cake. Primary drying removes free ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, although some water may remain as part of the solid. Cycle parameters depend on formulation, fill volume, vial type, and equipment performance.
The physical chemistry of freezing influences whether a formulation forms an amorphous glass or a crystalline solid. Amorphous systems can collapse if product temperature rises above the glass transition temperature of the freeze concentrate. Crystalline systems may show eutectic melting, where ice and solute melt together at a fixed temperature. Formulators add bulking agents, lyoprotectants, and buffers to preserve structure and biological activity. The optimum cycle keeps product temperature below critical thresholds during primary drying while allowing efficient sublimation.
Lyophilization is a dehydration technique in which a product is frozen and the solvent is removed under reduced pressure. The low pressure allows ice to sublimate directly into vapor without passing through a bulk liquid phase. This differs from conventional drying, where heat drives evaporation and can damage heat-sensitive structures. The process is used for biological materials, pharmaceutical formulations, and some foods. Its main advantage is preservation of porous structure and rapid reconstitution.
Freezing is the first stage and sets the ice structure that later becomes the pore network. The formulation is cooled below its freezing point, often with a controlled ramp, and solutes concentrate as ice forms. Primary drying then lowers chamber pressure and supplies heat to sublime the ice. The product temperature must stay below its collapse or eutectic temperature to prevent structural loss. Secondary drying raises the temperature modestly to remove bound water and achieve a low residual moisture.
A freeze-dryer consists of a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. Vials, ampoules, or bulk trays hold the product during the cycle. The condenser traps water vapor as ice at a temperature lower than the product. Cycle development balances shelf temperature, chamber pressure, and time. Scale-up can be difficult because heat and mass transfer change with equipment size, so process analytical tools and conservative validation are often used.
=== Fl–Fu === Louis B. Flexner (1902–1996). American biochemist at the University of Pennsylvania, who worked on the biochemistry of memory and brain function. Member Natl. Acad. Sci. USA. Otto Folin (1867–1934). Swedish-American chemist at Harvard, best known for developing methods for the determination of the constituents of protein-free blood filtrates. Member Natl. Acad. Sci. USA. Karl August Folkers (1906–1997). American biochemist at Merck, known for work on the antibiotics cathomycin and cycloserine. Ivar Asbjørn Følling (1888–1973). Norwegian biochemist and geneticist who first described phenylketonuria. Sidney W. Fox (1912–1998). American biochemist at the University of Miami who worked on the production of amino acids in abiotic conditions. Heinz Fraenkel-Conrat (1910–1999). German-American biochemist at UC Berkeley, known for research on viruses such as tobacco mosaic virus. Member Natl. Acad. Sci. USA. Rosalind Franklin (1920–1958). British X-ray crystallographer at King's and Birkbeck Colleges, London, who worked on the structure of DNA Perry A. Frey (b. 1935). American biochemist at the University of Wisconsin known for work on enzyme mechanisms. Member Natl. Acad. Sci. USA. Irwin Fridovich (1929–2019). American biochemist at Duke University, who discovered superoxide dismutase and studied its mechanisms and superoxide toxicity. Member Natl. Acad. Sci. USA. Joseph S. Fruton (1912–2007). Polish-American biochemist at the Rockefeller Institute.
=== Metric ounce === A metric ounce is an approximation of the imperial ounce, US dry ounce, or US fluid ounce. These three customary units vary. However, the metric ounce is usually taken as 25 or 30 ml (0.88 or 1.06 imp fl oz; 0.85 or 1.01 US fl oz) when volume is being measured, or in grams when mass is being measured. The US Food and Drug Administration (FDA) defines the "food labeling ounce" as 30.0 ml (1.06 imp fl oz; 1.01 US fl oz), slightly larger than the 29.6 ml (1.04 imp fl oz; 1.00 US fl oz) fluid ounce. Several Dutch units of measurement have been replaced with informal metric equivalents, including the ons or ounce. It originally meant 1⁄16 of a pound, or a little over 30 g (1.1 oz) depending on which definition of the pound was used, but was redefined as 100 g (3.5 oz) when the country metricated.
However, wildlife has much less PFOA than humans, unlike PFOS and other longer perfluorinated carboxylic acids; in wildlife, PFOA is not as bioaccumulative as longer perfluorinated carboxylic acids. Municipal wastewater and landfill leachates are considered as important sources of PFOA to the environment. Most industrialized nations have average PFOA blood serum levels ranging from 2 to 8 parts per billion; the highest consumer sub-population identified was in Korea—with about 60 parts per billion. In Peru, Vietnam, and Afghanistan blood serum levels have been recorded to be below one part per billion. In 2003–2004 99.7% of Americans had detectable PFOA in their serum with an average of about 4 parts per billion, and concentrations of PFOA in US serum have declined by 25% in recent years. Despite a decrease in PFOA, the longer perfluorinated carboxylic acid PFNA is increasing in the blood of US consumers. PFAS are also found in paper mill residuals, digestates, composts, and soils. Given the ubiquity of PFAS, and the comparative background levels which may be found in wastewater, biosolids, and leachates, setting requirements near analytical detection limits on these sources may not provide a discernable benefit to protecting public health.
Sources: en.wikipedia.org
== Fabrication == Fabrication of DNA origami objects requires a preliminary intuition of 3-dimensional DNA structural design. This can be difficult to grasp due to the complexity of exclusively using adenine-thymine pairings and guanine-cytosine pairings to both fold and unravel double helical DNA molecules such that the output strands produce uniquely desired shapes. The design software and the choice of base-pair sequences become crucial for creating intricate 2D or even 3D shapes as the key to DNA origami lies in the precise base-pairing between the technique's two building blocks: staple strands and the scaffold. This ensures specific binding and accurate folding. A scaffold strand is a long, single-stranded DNA molecule, often sourced from a virus. Staple strands are shorter DNA strands designed to bind to specific sequences on the scaffold strand, dictating its folding. To produce a desired shape, images are drawn with a raster fill of a single long DNA molecule. This design is then fed into a computer program that calculates the placement of individual staple strands. Each staple binds to a specific region of the DNA template, and thus due to Watson–Crick base pairing, the necessary sequences of all staple strands are known and displayed. The DNA is mixed, then heated and cooled. As the DNA cools, the various staples pull the long strand into the desired shape. Designs are directly observable via several methods, including electron microscopy, atomic force microscopy, or fluorescence microscopy when DNA is coupled to fluorescent materials.
=== Roads === The A34 road, which links Salford and Winchester, by-passes the town centre to the east; this was later extended around neighbouring Alderley Edge. It joins the A555 at Handforth Dean, which has been extended to Manchester Airport.
==== Xbox reception ==== The Xbox edition received mixed reviews from critics in comparison to the original game. On the topic of graphics, Matthew Kato from Game Informer wrote that there were "graphical updates here and there" and mentioned the game's inclusion of weather. Greg Kasavin of GameSpot felt that the visuals weren't extraordinary and not enough to make the game "good-looking". IGN's Aaron Boulding mentioned that they were "the biggest disappointment". He commented that the environments were noteworthy in design, but "not in their overall look and level of detail". The AI technology was a surplus for the Xbox edition, because of critics praising for its human-like behavior. Kato mentioned that the bot AI contained some "human-esque traits" and that it would start to understand the map after some rounds. Kasavin found it surprising that the bots weren't following real-life tactics of terrorists or counter-terrorists, but rather mimic the actions of a player. He pointed out that they would camp at a certain place and follow the orders of a player, such as following them or holding a position. Many critics also highlighted Xbox Live as one of the main reasons to purchase the game. Kasavin noted that it runs properly, with hosted matches able to hold 10 players. Boulding expressed that "online play over Xbox Live is going to be the greatest reason to buy this game" and that it's convenient.
Sources: en.wikipedia.org
As part of supply provisions within the Comecon, Lot was allocated four Il-86s as barter for component manufacture; the airline deferred deliveries which were cancelled by 1987. In 1988 the East German airline Interflug is said to have prepared to take delivery of two Il-86s and to have allocated them the registrations DDR-AAA and DDR-AAB. Instead, that same year the airline took delivery of two Airbus A310s. The sole export order for the Il-86 − and the sole commercial transactions involving factory-built rather than secondhand examples − was by China Xinjiang Airlines which received three aircraft in 1990. The first Il-86 to be built was displayed at the Paris Salon International de l'Aéronautique in 1977. It was noted that its interior used patented fire-resistant materials and hydraulics employed a fire-resistant fluid. At that time a version without the "luggage at hand" system was offered, seating 375 or alternatively weighing 3,000 kg (6,600 lb) less and having longer range. This version offered 7% lower seat-mile operational costs. The type was again displayed at Paris in 1979, 1981, 1983 and 1985, the Farnborough Air Show in 1984 and other world air events. Setting records was a traditional Soviet way of promoting aviation products. On Tuesday September 22, 1981, an Il-86 flown by Commander G Volokhov and Second Pilot A Tyuryumin set Fédération Aéronautique Internationale records for flying payloads of 35, 40, 45, 50, 55, 60 and 65 tonnes over a 2,000 km closed circuit at an average of 975.3 km per hour.
macronucleus Also meganucleus. The larger of the two types of nuclei which occur in pairs in the cells of some ciliated protozoa. Macronuclei are highly polyploid and responsible for directing vegetative reproduction, in contrast to the diploid micronuclei, which have important functions during conjugation.
Up to this point, Counterparts and Test for Echo were two of Rush's most guitar-driven albums. The latter album also includes elements of jazz and swing-style drumming by Peart, which he had learned from drum coach Freddie Gruber during the interim between Counterparts and Test for Echo. "Stick It Out" from Counterparts reached the summit of the US Mainstream Rock Tracks Chart, with the album peaking at No. 2 in the US and No. 6 in Canada. Test for Echo reached the Top 5 in both countries, with the title track again topping the US Mainstream Rock Tracks Chart. In October 1996, in support of Test For Echo, the band embarked on a North American tour, the band's first without an opening act and dubbed "An Evening with Rush". The tour was broken into two segments, spanning October through December 1996 and May through July 1997. After the conclusion of the Test for Echo tour in 1997, the band entered a five-year hiatus primarily due to personal tragedies in Peart's life. Peart's daughter Selena died in a car crash in August 1997, and his wife Jacqueline died of cancer in June 1998. Peart went on hiatus to mourn and reflect. During that time, he travelled extensively throughout North America on his BMW motorcycle, covering 88,000 km (55,000 mi). In his book Ghost Rider: Travels on the Healing Road, Peart writes of how he had told his bandmates at Selena's funeral, "consider me retired." This left the band's future uncertain, and Lee and Lifeson prepared an archival album, Different Stages, for release during the hiatus.
== Stock exchange listing and later history == Mondobiotech's common shares began trading on the SIX Swiss Exchange on 26 August 2009 under the symbol RARE. The first day's closing price was CHF 392. SIX records a market capitalization of approximately CHF 490 million in its historical listing data. In its account of the listing, the Swiss business magazine BILANZ reported an implied value of approximately CHF 2.6 billion for the entire company at the first-day closing price, noting that only a small number of shares had traded that day. No new shares were issued as part of the initial listing. BILANZ reported in 2011 that the company had accumulated losses and had not yet brought a medicine to market. Mondobiotech changed its name to THERAMetrics in June 2013 and completed its combination with Pierrel Research International in September 2013. THERAMetrics subsequently combined with Relief Therapeutics SA and changed its corporate name to Relief Therapeutics Holding AG in July 2016.
Sources: en.wikipedia.org
Lyophilization relies on sublimation, so water moves from solid ice to vapor without becoming liquid. The material is frozen, pressure is reduced, and controlled heat is supplied. Vapor is captured on a cold condenser, leaving a dry porous solid.
The process has three main stages: freezing, primary drying, and secondary drying. Freezing sets the ice structure, primary drying removes free ice, and secondary drying removes bound water. Each stage uses specific temperature, pressure, and time settings.
No, it is a drying method rather than a sterilization method. Removing water can limit microbial growth, but it does not reliably kill microorganisms. Sterility must come from separate steps such as filtration, heat treatment, or aseptic processing.
Lyophilization removes water by sublimation from a frozen material, while evaporation changes liquid water into vapor. The low-pressure freezing step avoids the liquid phase and can preserve heat-sensitive structures.