Everything below concerns sublimation. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-02-13. Where a claim depends on a specific study, the study is described rather than over-claimed.
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 process that removes water from a frozen material by sublimation under low pressure. The material is first frozen so that water becomes ice; then the surrounding pressure is lowered below the vapor pressure of ice. Heat is applied gently so ice changes directly to vapor without passing through a bulk liquid phase. The vapor is collected on a cold condenser, leaving a dry porous matrix. This process differs from simple evaporation because the material remains frozen during the main drying stage.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilisation is the British spelling; the process is not simple evaporation. |
| Primary drying pressure | 0.05–0.3 mbar | Pressure must remain below the vapor pressure of ice at the product temperature. |
| Sublimation temperature | Below 0 °C | Ice changes directly to vapor while the product remains frozen. |
| Typical shelf temperature | −40 to −10 °C | Exact setting depends on formulation critical temperature and equipment. |
| Cycle duration | 12–72 hours | Time varies with fill volume, formulation, and dryer performance. |
Formulation composition influences whether freeze-drying produces an intact cake or a collapsed mass. Excipients such as sugars and polymers can raise the collapse temperature and provide bulk during drying. The critical temperature for primary drying is often the collapse temperature or the glass transition temperature of the maximally concentrated phase. If the product temperature exceeds this threshold, the frozen matrix may soften and lose structure. Established practice therefore links shelf temperature and chamber pressure to the formulation's thermal properties.
The physics of freeze-drying couples heat transfer, mass transfer, and phase change. Heat supplied through the shelf must reach the sublimation front without melting the ice or degrading the product. Water vapor then travels through the already dried layer and leaves the chamber, where low pressure and cold traps keep it from returning. The dried layer acts as a resistance to vapor flow, so drying rate changes as the front recedes. Open questions remain about how pore structure and formulation heterogeneity affect drying uniformity at larger scales.
Lyophilization removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts liquid water into ice and concentrates dissolved solids. Primary drying then lowers chamber pressure so ice changes directly into vapor without passing through a liquid phase. Secondary drying raises the shelf temperature to remove bound water that remains after ice sublimation. The result is a dry, porous structure that can be reconstituted later.
Lyophilization is a drying process in which a solvent, usually water, is removed from a frozen material by sublimation under reduced pressure. The material is first solidified, then placed under vacuum so that ice transitions directly to vapor without a bulk liquid phase. This approach suits heat-sensitive substances that would degrade during conventional evaporation. Primary drying removes unbound ice, while secondary drying reduces water that remains adsorbed to the solid matrix. The result is a porous, lightweight solid that can be reconstituted later.
A typical cycle begins with freezing, sometimes including an annealing step to control ice crystal size. Freezing conditions influence the pore network that later allows vapor escape. During primary drying, shelf temperature and chamber pressure are set so heat enters the product while its temperature stays below the collapse or eutectic point. Secondary drying then raises the shelf temperature to desorb bound water and lower residual moisture. Cycle design depends on formulation, fill volume, container type, and equipment capability.
Freezing determines ice crystal structure and pore size, which affect drying speed and product uniformity. Rapid freezing creates small crystals, while slow freezing creates larger crystals and often faster sublimation. During primary drying, chamber pressure is held below the vapor pressure of ice, and shelf temperature supplies heat for sublimation. The ice front recedes, leaving a porous matrix. Thermal limits such as collapse and eutectic temperatures set safe boundaries for formulation. These limits vary with solute composition and concentration.
Secondary drying removes bound water that remains after ice sublimation. Shelf temperature is raised gradually while pressure remains low, reducing water content to a target range. Over-drying can cause brittleness or electrostatic issues, while under-drying affects stability. The endpoint is often judged by pressure rise tests, temperature measurements, or water content analysis. Scale-up depends on matching heat and mass transfer across equipment sizes. Small changes in shelf temperature or pressure can alter cycle length substantially.
Lyophilization, or freeze-drying, removes water from a material by freezing it and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intervening liquid state. It is used for heat-sensitive materials that would degrade in conventional drying. The three stages are freezing, primary drying, and secondary drying, each with distinct temperature and pressure requirements. In practice, cycle design balances these variables.
Lyophilization, also called freeze-drying, removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts free water into ice and may also produce a glassy phase. Primary drying then lowers chamber pressure so ice sublimes directly to vapor without passing through a liquid stage. Secondary drying raises the temperature modestly to remove bound water. The result is a porous, dry solid that usually reconstitutes quickly. Each stage influences pore structure, residual moisture, and stability.
The physics of lyophilization depends on phase boundaries and heat and mass transfer. During primary drying, heat supplied to the product must equal the latent heat of sublimation, while water vapor moves through the drying cake to the condenser. If shelf temperature or pressure is set too high, the ice front can exceed the collapse temperature, causing meltback or pore collapse. If conditions are too cold, drying slows and costs rise. Formulation excipients, vial geometry, and freezing rate alter these limits.
Equipment for lyophilization includes a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. A refrigeration system cools the shelves and condenser below the product's freezing point. Process monitoring often uses Pirani and capacitance manometers, thermocouples, and resistance sensors. Cycle development balances product quality with time and energy use. Some products are annealed during freezing to improve crystallization of bulking agents. Open questions remain about scaling cycles between laboratory, pilot, and production freeze-dryers.
Delta cells (δ-cells or D cells) are somatostatin-producing cells. They can be found in the stomach, intestine and the pancreatic islets. Delta cells comprise ca 5% of the cells in the islets but may interact with many more islet cells than suggested by their low numbers. In rodents, delta-cells are located in the periphery of the islets; in humans the islet architecture is generally less organized and delta-cells are frequently observed inside the islets as well. In both species, the peptide hormone Urocortin III (Ucn3) is a major local signal that is released from beta cells (and alpha cells in primates) to induce the local secretion of somatostatin. It has also been suggested that somatostatin may be implicated in insulin-induced hypoglycaemia through a mechanism involving SGLT-2 receptors. Ghrelin can also strongly stimulate somatostatin secretion, thus indirectly inhibiting insulin release. Viewed under an electron microscope, delta-cells can be identified as cells with smaller and slightly more compact granules than beta cells. The δ-cells in the stomach contain CCKBR (which respond to gastrin) and M3 receptors (which respond to Ach). Respectively, these receptors will increase somatostatin output and decrease somatostatin output from the δ-cells. VIP, vasoactive intestinal peptide, acts positively on δ-cells resulting in more somatostatin being released.
==== Acid pigmentation ==== In 2009 Luigi Garlaschelli, professor of organic chemistry at the University of Pavia, stated that he had made a full-size reproduction of the Shroud of Turin using only medieval technologies. His cloth was woven in the exact same manner and herringbone pattern by yarn type and weight as the Shroud. Garlaschelli placed a linen sheet over a volunteer and then rubbed it with an acidic pigment for the body. The shroud was then aged in an oven before being washed to remove the pigment. He then added blood stains, scorches and water stains to replicate the original. Giulio Fanti, professor of mechanical and thermic measurements at the University of Padua, commented that "the technique itself seems unable to produce an image having the most critical Turin Shroud image characteristics". Garlaschelli noted that the microscopic properties of his reproductions can't be exactly identical to the original, as accelerated and artificial aging lasting 4 hours cannot replicate the natural centuries the Shroud of Turin has gone through. He therefore considered the criticisms of those who claim a need for an absolute similarity as specious. Garlaschelli's reproduction was shown in a 2010 National Geographic documentary. Garlaschelli's technique included the bas-relief approach (described below) but only for the image of the face. The resultant image was visibly similar to the Turin Shroud, though lacking the uniformity and detail of the original.
In the 2010s, Ells tried to diversify the company by creating or acquiring several subsidiaries. These subsidiaries offered very different cuisines compared to their parent company. Examples include soul food (Soul Daddy), Asian cuisine (ShopHouse Southeast Asian Kitchen), pizza (Pizzeria Locale), and burgers (Tasty Made). In 2023, Chipotle had also tried incorporating California-inspired bowls into the Farmesa Fresh Eatery concept. The few test locations were not a financial success, and all concepts were discontinued. In 2011, Steve Ells was a judge for the TV show America's Next Great Restaurant and investor of ANGR Holdings, the company that would launch the winning concept's restaurants. Chipotle agreed to purchase Ells' investment in ANGR at his cost, provide support for ANGR operations, and invest a total of $2.3 million in cash contributions. The winning concept, Soul Daddy, was quickly closed after operating for eight weeks. In September 2011, Chipotle opened an Asian fast-casual concept restaurant named ShopHouse Southeast Asian Kitchen in Washington, D.C. The company said the new restaurant "would follow the Chipotle service format and its focus on 'food with integrity' in ingredients". Chipotle's plan was to start with only one store and see how the restaurant worked out before expanding the concept. On July 29, 2016, the company announced the opening of its first Tasty Made burger restaurant in the fall.
== External links == Sir Howard Florey on Nobelprize.org including the Nobel Lecture, "Penicillin", 11 December 1945 Oral History: Sir Howard Florey—Interviewed by Hazel de Berg in 1967 (audio recording)
There are three amino acids with side chains that are cations at neutral pH: arginine (Arg, R), lysine (Lys, K) and histidine (His, H). Arginine has a charged guanidino group and lysine a charged alkyl amino group, and are fully protonated at pH 7. Histidine's imidazole group has a pKa of 6.0, and is only around 10% protonated at neutral pH. Because histidine is easily found in its basic and conjugate acid forms it often participates in catalytic proton transfers in enzyme reactions.
Sources: en.wikipedia.org
A major focus in the field of protein engineering is on creating DNA libraries that sample regions of sequence space, often with the goal of finding mutants of proteins with enhanced functions compared to the wild type. These libraries are created either by using a wild type sequence as a template and applying one or more mutagenesis techniques to make different variants of it, or by creating proteins from scratch using artificial gene synthesis. These libraries are then screened or selected, and ones with improved phenotypes are used for the next round of mutagenesis. Protein Sequence space Directed evolution Protein engineering High-dimensional space
The enthalpy of sublimation, measured through testing of fermium alloys, is calculated at 33.8±3 kcal/mol (141.4±12.6 kJ/mol) derived from Second Law values, and 34.8 kcal/mol (145.6 kJ/mol) derived from Third Law values, both at 298 K. Through this, fermium is considered a divalent metal.
30 October – A study finds that the world's remaining carbon budget for 1.5 °C of global warming is only half that of previous estimates, at less than 250 gigatonnes of carbon dioxide, or around six years of annual worldwide emissions. 31 October The first discovery of a virus, phage MiniFlayer, that attaches to another helper virus is reported. The coalition of research organizations and science funders behind Plan S publishes a proposal for moving scholarly communication towards open science practices that are more transparent, accessible, efficient and without author fees. Hazard research is published: a study further confirms noncompensable moist heat extremes will be beyond bounds of past human evolutionary environments for billions of people (9 Oct), an analysis calls for health policy regarding unhealthy ultra-processed foods (9 Oct), an analysis calls for action regarding the summarized environmental footprint of bitcoin mining (9 Oct), a global assessment of risk from increasing pollinator loss to crop pollination shows cocoa and coffee at high risk (12 Oct), a training data poisoning technique, 'Nightshade', against generative AI software specific to select prompts is described (20 Oct), a study indicates low deep sleep percentage is a modifiable dementia risk factor (30 Oct).
=== High-salt liquid-state fermented soy sauce === High-salt liquid-state fermentation (HLF) of soybeans depends heavily on microbial activity, metabolism and enzymatic hydrolysis of macronutrients. Most traditional approaches fall into the scope of HLF.
Sources: en.wikipedia.org
microvillus A small, slender, tubular cytoplasmic projection, generally 0.2–4 micrometres long and 0.1 micrometres in diameter, protruding from the surface of some animal cells and supported by a central core of microfilaments. When present in large numbers, such as on epithelial cells lining the respiratory and alimentary tracts, they form a dense brush border which presumably serves to increase each cell's absorptive surface area.
== Research == Polyphenols are a large, diverse group of compounds, which makes it challenging to determine their biological effects. They are not considered nutrients, as they do not contribute to growth, survival, or reproduction, nor do they provide dietary energy. Therefore, they do not have recommended daily intake levels, such as those for macronutrients and micronutrient (vitamins and minerals). In the United States, the Food and Drug Administration issued guidance to manufacturers that polyphenols cannot be mentioned on food labels as antioxidant nutrients unless physiological evidence exists to verify such a qualification and a Dietary Reference Intake value has been established – characteristics which have not been determined for polyphenols. In the European Union, two health claims were authorized between 2012 and 2015: 1) flavanols in cocoa solids at doses exceeding 200 mg per day may contribute to maintenance of vascular elasticity and normal blood flow; and 2) olive oil polyphenols (5 mg of hydroxytyrosol and its derivatives such as oleuropein complex and tyrosol) may "contribute to the protection of blood lipids from oxidative damage", if consumed daily. As of 2022, clinical trials that assessed the effect of polyphenol-rich diets on health biomarkers are limited, with results difficult to interpret due to the wide variation of intake values for both individual polyphenols and total polyphenols. Polyphenols were once considered as antioxidants, but this concept is obsolete.
=== 18 June === Ukrainian forces retook the village of Tykhe, west of Vovchansk. In Russia, the governor of Rostov Oblast claimed that several oil storage tanks were set on fire by a drone strike in Azov that destroyed 5,000 cubic metres of petroleum products. An oil depot in Krasnodar Krai was struck by Neptune missiles according to local sources, damaging a pipeline, “technical facilities” and starting a fire. No casualties were reported. A Ukrainian court sentenced a resident of Donetsk Oblast to 15 years' imprisonment for spying on Ukrainian positions on behalf of Russia during the Battle of Bakhmut. Swiss authorities claimed to have foiled an assassination attempt aimed at the Ukrainian peace summit, saying that a Russian diplomat was arrested a “few weeks” prior after trying to buy firearms. Ukrainian military observer Kostyantyn Mashovets claimed that the Russian Central Grouping of Forces has about 87,000 personnel, 365 tanks, 864 armored combat vehicles, of which about 68,000-70,000 personnel, 310-320 tanks, and about 576 armored fighting vehicles are currently deployed in the Pokrovsk direction.
Sources: en.wikipedia.org
The main change is sublimation, in which ice becomes water vapor without melting into liquid water. This occurs when the chamber pressure is held below the vapor pressure of ice while mild heat is supplied. The result is a dry, porous solid that retains much of its original shape.
Freezing determines ice crystal size, solute distribution, and the pore network left after drying. A slow or fast freezing rate can produce different cake structures and affect reconstitution. It also sets whether the formulation follows an amorphous or crystalline drying path.
It removes most free water during primary drying and part of the bound water during secondary drying. A small residual moisture content often remains and is specified for each product. Complete removal is generally neither practical nor desirable for stability.
Yes, the terms are generally interchangeable. Lyophilization is more common in pharmaceutical and laboratory contexts, while freeze-drying appears widely in food science and general writing. Both describe removal of solvent by sublimation under vacuum after freezing.