If you have been reading about Collapse temperature and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-01-28. Where a claim depends on a specific study, the study is described rather than over-claimed.
A typical cycle begins with freezing, which fixes the material into a solid and determines ice crystal size. Primary drying then raises heat under vacuum so ice sublimes, often near or below the collapse temperature of the formulation. Secondary drying removes bound water that remains after ice is gone, usually by gently warming the product. Each stage balances heat input against pressure to avoid melting or structural damage. Temperature probes and pressure sensors guide the transition between stages.
In practice, lyophilization is slower and more energy intensive than simple drying. Cycle times can range from hours to several days depending on load, container, and formulation. Amorphous materials may require excipients that help preserve structure during freezing and drying. The method is widely used for biological materials, pharmaceuticals, and foods where heat drying would cause unacceptable change. Open questions remain about scaling cycles between laboratory and production equipment, and this gap affects technology transfer.
Quality control for freeze-dried lots combines visual inspection with instrumental tests. Cake appearance, color, and shrinkage are recorded against a reference, while residual moisture is measured by Karl Fischer titration or loss on drying. Thermal analysis can reveal phase transitions and crystallization events, and X-ray diffraction distinguishes amorphous from crystalline solids. Microbiological tests and container closure integrity checks are also routine for sterile products. Analytical methods must be validated for the matrix, because excipients and low moisture can affect accuracy. Open questions include how best to predict long-term stability from short-term data.
Lyophilized solids are often hygroscopic, so handling occurs in controlled low-humidity areas or glove boxes when the material is exposed. Vials remain sealed with elastomeric stoppers and aluminum crimps until use, because airborne moisture can raise residual water and shorten shelf life. The porous cake is fragile and may crack, shrink, or powder during transport. Personnel typically avoid repeated warming and cooling of sealed units, which can draw moisture through closures. These practices aim to preserve the low water content achieved during drying.
| Property | Value | Notes |
|---|---|---|
| Common synonym | Freeze-drying | Same dehydration operation |
| Typical vacuum | 10-100 Pa | Pressure during primary drying |
| Primary drying temperature | -40 to -10 °C | Below collapse temperature for many formulations |
| Cycle duration | 12-72 hours | Varies with load, container, and formulation |
| Key phase change | Sublimation | Solid ice to water vapor |
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.
Analytical methods for lyophilized solids must account for the low moisture content and the fragile cake. Karl Fischer titration is widely used for water content, while near-infrared spectroscopy can measure moisture non-destructively in sealed containers. X-ray diffraction and modulated differential scanning calorimetry help identify crystalline or amorphous phases. Residual solvent analysis may be needed if organic solvents were used during formulation. The combination of these methods supports batch release and long-term stability assessment.
Lyophilized products are typically stored as sealed solids in vials or syringes. Moisture ingress is a major concern because many dried cakes are hygroscopic and can lose stability when exposed to humid air. Storage temperature depends on the formulation; some products are kept refrigerated, while others are stable at room temperature. Container closure integrity and headspace moisture are often monitored. Light protection may also be required for some photosensitive materials.
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.
Desiccation (drought) stress is defined as conditions where water becomes the growth limiting factor. MAAs have been reportedly found in high concentrations in many microorganisms exposed to drought stress. Particularly cyanobacteria species that are exposed to desiccation, UV radiation and oxidation stress have been shown to possess MAA's in an extracellular matrix. However it has been shown that MAAs do not provide sufficient protection against high doses of UV radiation. Thermal (heat) stress is defined as temperatures lethal or inhibitory towards growth. MAA concentrations have been shown to be up-regulated when an organism is under thermal stress. Multipurpose MAAs could also be compatible solutes under freezing conditions, because a high incidence of MAA producing organisms have been reported in cold aquatic environments.
=== 2019 Seattle, Washington, United States === Thirteen people were exposed to caesium-137 in May 2019 at the Research and Training building in the Harborview Medical Center complex in Seattle, Washington. A contract crew was transferring the caesium from the lab to a truck when the powder was spilled. Five people were decontaminated and released, but eight who were more directly exposed were taken to the hospital while the research building was evacuated.
== Intellectual Property == In May 2013, Boehringer Ingelheim of Germany applied for a Methods of Treatment, Pharmaceutical Compositions and uses thereof patent. This patent application included SGLT2 inhibitor ipragliflozin. In April 2014, Boehringer Ingelheim applied for usage of SGLT2 inhibitors in equine animals. The usage of these inhibitors in an animal study allows for progression in the application in humans for more than just diabetes. The National Institute of Biological Science out of Beijing filed a similar patent in September 2015. In January 2016, the Dalian University of Technology filed a patent on the synthetic method of ipragliflozin. There are additional patents for the synthesis of the intermediates leading up to these types of inhibitors.
[...] if the Russian Federation's Ministry of Defense did not publish such data [indicating the timeline of Russian military activities], then the suspicion grows elsewhere that perhaps they are covering something up such as the exact times they moved." Thomas contended that it was "likely" Saakashvili did not intend to use force "until he was cornered by events." Thomas stated that analysts saw the Russian activities in Abkhazia before August 2008 "as a deception operation to draw attention away from preparations underway in South Ossetia." Thomas criticized the Russian research The Tanks of August because it "omitted crucial meetings and attempts of Georgia to avoid conflict and none of the events were documented with footnotes." Thomas noted, "Russia refused to negotiate with Georgia in the crucial days before conflict erupted. [...] Artillery duels were heavier than in the past, and some artillery positions were located behind Russian peacekeeping forces in South Ossetia." Thomas further stated, "The conclusion that many analysts have reached is that the actions of the Russians were preplanned and that they drew the Georgians into a decision dilemma: either act or lose territory. [...] One of the problems with the Russian version of events is that it ignores all of the positive things Georgia did to prevent fighting from ever breaking out." In 2012, Rick Fawn and Robert Nalbandov wrote that "the precise timing of events on the night of 7–8 August 2008 is a substantial study in itself, and depends on all of the inputs being provable.
=== Adaptive immunity === Activated platelets are able to participate in adaptive immunity, interacting with antibodies. They are able to specifically bind IgG through FcγRIIA, a receptor for IgG's constant fragment (Fc). When activated and bound to IgG-opsonised bacteria, platelets release reactive oxygen species (ROS), antimicrobial peptides, defensins, kinocidins and proteases, killing the bacteria directly. Platelets also secrete proinflammatory and procoagulant mediators such as inorganic polyphosphates or platelet factor 4 (PF4), connecting innate and adaptive immune responses.
Sources: en.wikipedia.org
== Role in cancer == Lazaris-Karatzas et al. found that that over-expressing eIF4E causes tumorigenic transformation of fibroblasts. Since this initial observation, numerous groups have recapitulated these results in different cell lines. As a result, eIF4E activity is implicated in several cancers including cancers of the breast, lung, and prostate. In fact, transcriptional profiling of metastatic human tumors has revealed a distinct metabolic signature wherein eIF4E is known to be consistently up-regulated. eIF4E levels are increased in many cancers including acute myeloid leukemia (AML), multiple myeloma, infant ALL, diffuse large B-cell lymphoma, breast cancer, prostate cancer, head and neck cancer and its elevation generally correlates with poor prognosis. In many of these cancers such as AML, eIF4E is enriched in nuclei and several of eIF4E's activities are found to be elevated in primary patient specimens, including capping, splicing, RNA export, and translation. In the first clinical trials targeting eIF4E, old antiviral drug ribavirin was used as a m7G cap competitor which had substantial activity in cancer cell lines and animal models associated with dysregulated eIF4E. To date PubMed searches reveal that over 30 groups have found that ribavirin targets eIF4E activity while two did not. In the first trial to ever target eIF4E, ribavirin monotherapy was demonstrated to inhibit eIF4E activity leading to objective clinical responses including complete remissions in AML patients.
=== San Antonio Nathan Shock Center === The San Antonio Nathan Shock Center (NSC) is one of only eight National Institute on Aging (NIA)-funded Nathan Shock Centers of Excellence in the Basic Biology of Aging in the United States. Since its establishment in 1995, the Center has served as an internationally recognized resource dedicated to advancing the fundamental biology of aging and accelerating the development of interventions that promote healthy aging and extend healthspan. The overarching mission of the Center is to identify the molecular, cellular, and physiological mechanisms that drive the aging process and translate these discoveries into strategies that delay or prevent age-associated diseases and functional decline. The San Antonio Nathan Shock Center provides investigators with an integrated, "one-stop-shop" research infrastructure that supports every stage of aging research—from experimental design and animal model development to functional phenotyping, pathology, metabolism, pharmacology, and data interpretation. This comprehensive approach enables investigators to conduct rigorous, multidisciplinary studies that examine lifespan, healthspan, and the biological mechanisms underlying aging. By integrating specialized expertise and state-of-the-art technologies within a single research environment, the Center accelerates scientific discovery while promoting collaboration among investigators locally, nationally, and internationally. The Center is organized around six highly integrated research cores that provide specialized services and scientific expertise.
How the sample and matrix is deposited on the surface of the sample probe needs to be a consideration in sample preparation as well. The dried drop method is the simplest of deposition methods. The matrix and sample solution are mixed together and then a small drop of the mixture is placed on the sample probe surface and allowed to dry, thus crystallizing. The sandwich method involves depositing a layer of matrix onto the surface of the probe and allowing it to dry. A drop of the sample followed by a drop of additional matrix is then applied to the layer of dried matrix and allowed to dry as well. Variations on the sandwich technique involve depositing the matrix on the surface and then depositing the sample directly on top of the matrix. A particularly useful method involves depositing the matrix solution on the surface of the sample probe in a solvent that will evaporate very rapidly, thus forming a very thin fine layer of matrix. The sample solution is then placed on top of the matrix layer and allowed to evaporate slowly, thus integrating the sample into the top layer of matrix as the sample solution evaporates. An addition concern when depositing the sample on the surface of the probe is the solubility of the sample in the matrix. If the sample is insoluble in the matrix, additional methods must be employed. A method used in this case involves mechanical grinding and mixing of solid sample and solid matrix crystals. Once blended well, this powder can be deposited on the surface of the sample probe in free powder form or as a pill.
in the version dated April 30, 2003 - that their specialist knowledge in radiation protection has been updated and must complete a full-day course with a final examination. Specialist knowledge in radiation protection is required by the Technical Knowledge Guideline according to X-ray Ordinance. - R3 for persons who work with baggage screening equipment, industrial measuring equipment and interfering emitters. Since 2019, the regulatory areas of the previous X-ray and radiation protection ordinances have been merged in the amended Radiation Protection Ordinance. The Radiation Protection Commission (SSK) was founded in 1974 as an advisory body to the Federal Ministry of the Interior. It emerged from Commission IV "Radiation Protection" of the German Atomic Energy Commission, which was founded on January 26, 1956. After the Chernobyl nuclear disaster in 1986, the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection was established in the Federal Republic of Germany. The creation of this ministry was primarily a response to the perceived lack of coordination in the political response to the Chernobyl disaster and its aftermath. On December 11, 1986, the German Bundestag passed the Precautionary Radiation Protection Act (StrVG) to protect the population, to monitor radioactivity in the environment, and to minimize human exposure to radiation and radioactive contamination of the environment in the event of radioactive accidents or incidents. The last revision of the X-Ray Ordinance was issued on January 8, 1987.
Sources: en.wikipedia.org
The finding consists of a single bone fragment about 2 cm long that was unearthed in 2012 by Russian archeologists at the Denisova Cave from layer 12 of the East Gallery. The cave is located in Denisova valley, Altai Mountains in Siberia, Russia. At the time, the origin of the bone fragment remained unknown because it was archived along with thousands of other nondescript bone fragments from the cave. In 2015, Tom Higham and Katerina Douka decided to try and apply new scientific methods to see whether they could be used to find human remains amongst the thousands of unidentified bone samples in the site. With the collaboration of the head excavators of the Denisova site; Michael Shunkov and Anatoly Derevianko, they took several bags containing thousands of unidentified bone fragments back to the University of Oxford. Samantha Brown, an MSc student at the University of Oxford, worked on the project as part of her dissertation research, screening more than 2000 bone fragments. Using Zooarchaeology by Mass Spectrometry (ZooMS) and working with the laboratory of Michael Buckley at the University of Manchester, they were able to compare the collagen protein fingerprints derived from the Denisova Cave bones to animals and humans of known origin, and they discovered that one of these bones (DC1227) belonged to an archaic human.
=== Family history and genetics === Positive family history is a risk factor for glaucoma. The relative risk of having primary open-angle glaucoma is increased about two- to four-fold for people who have a sibling with glaucoma. Glaucoma, particularly primary open-angle glaucoma, is associated with mutations in several genes, including MYOC, ASB10, WDR36, NTF4, TBK1, and RPGRIP1. Many of these genes are involved in critical cellular processes that are implicated in the development and progression of glaucoma, including regulation of intraocular pressure, retinal ganglion cell health, and optic nerve function. Normal-tension glaucoma, which comprises 30-90% of primary open-angle glaucoma (depending on ethnic group), is also associated with genetic mutations (including OPA1 and OPTN genes). Additionally, some rare genetic conditions increase the risk of glaucoma, such as Axenfeld-Rieger syndrome and primary congenital glaucoma, which is associated with mutations in CYP1B1 or LTBP2. They are inherited in an autosomal recessive fashion. Axenfeld-Rieger syndrome is inherited in an autosomal dominant fashion and is associated with PITX2 or FOXC1.
== Structure == The molecule is a 6-membered ring of alternating nitrogen and sulfur atoms, where each sulfur atom is attached to one chlorine atom by a single bond. The molecule contains alternating single and double bonds in the S3N3 core. The molecule has C3v symmetry. The S3N3 core is slightly ruffled structure with S-N distances of 160.5 pm. The S-Cl distances are 208 pm, and the chlorine atoms are mutually cis. The S centers are tetravalent and pyramidal. In contrast, with six fewer electrons, cyanuric chloride is a planar ring.
Virologist Angela Rasmussen described this problem as a quality control issue that is unimportant for healthy people because adenoviruses are not significant pathogens, but added that it could produce serious adverse effects in immunocompromised individuals. Medicinal chemist Derek Lowe commented that the presence of replicating adenoviruses is unlikely to cause any major problems, but it is a "completely unnecessary risk", that it certainly will harm some people, and that providing a product different from the one described in studies undermines the credibility of all manufacturing and quality control processes, adding that some posts on the official Sputnik V Twitter account constitute "aggressive political marketing" and some make invalid claims regarding the performance of competing vaccines, such as the Pfizer-BioNTech vaccine. Anvisa said that the import ban can be reversed if Gamaleya clarifies the issues. Adenovirus infections cause only mild colds in healthy individuals, but they can cause life-threatening illnesses in immunodeficient individuals. The director of the Public Health Institute of Chile (ISP), Heriberto Garcia, said that the ISP would not necessarily reject the vaccine, even if it had replicating adenoviruses, because the risk of getting a common cold from the vaccine must be weighed against the risk of contracting COVID-19 when not vaccinated. He also said that real-world data from Argentina and Mexico showed no adverse effects greater than those seen in people vaccinated with the Pfizer-BioNTech vaccine or CoronaVac.
facilitative transporters (allow solutes to flow downhill with their electrochemical gradients) secondary active transporters (allow solutes to flow uphill against their electrochemical gradient by coupling to transport of a second solute that flows downhill with its gradient such that the overall free energy change is still favorable) The SLC series does not include members of transport protein families that have previously been classified by other widely accepted nomenclature systems including:
Sources: en.wikipedia.org
Primary drying removes ice by sublimation under vacuum. Secondary drying removes water that is bound to the material, often by warming the product after most ice has left. Both stages occur below temperatures that would cause unwanted melting.
Sublimation requires the solvent to remain solid so vapor leaves without passing through a liquid phase. If the product melts, the porous structure can collapse and drying becomes uneven. Maintaining frozen conditions preserves the intended physical form.
No, freeze-drying is a dehydration method, not a sterilization step. It can reduce water activity and limit microbial growth during storage, but it does not reliably kill microbes or remove endotoxins. Sterility must come from separate validated processes.
Karl Fischer titration is widely used because it is specific for water and works at low levels. Loss on drying is simpler but less specific, since volatile solvents or decomposition products can also be lost.