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Freeze drying

Freeze drying, also known as lyophilization or cryodesiccation, is a low temperature dehydration process that involves freezing the product and lowering pressure, thereby removing the ice by sublimation. This is in contrast to dehydration by most conventional methods that evaporate water using heat.

History
The Inca were freeze drying potatoes into chuño since the 13th century. The process involved multiple cycles of exposing potatoes to below freezing temperatures on mountain peaks in the Andes during the evening, and squeezing water out and drying them in the sunlight during the day. The Inca people also used the unique climate of the Altiplano to freeze dry meat. The Japanese koya-dofu, freeze-dried tofu, dates to the mid-1500s in Nagano and the 1600s on Mount Koya. Modern freeze drying began as early as 1890 by Richard Altmann who devised a method to freeze dry tissues (either plant or animal), but went virtually unnoticed until the 1930s. In 1909, L. F. Shackell independently created the vacuum chamber by using an electrical pump. No further freeze drying information was documented until Tival in 1927 and Elser in 1934 had patented freeze drying systems with improvements to freezing and condenser steps. Early uses in food Freeze-dried foods became a major component of astronaut and military rations. What began for astronaut crews as tubed meals and freeze-dried snacks that were difficult to rehydrate, were transformed into hot meals in space by improving the process of rehydrating freeze-dried meals with water. The complete nutrient profile was improved with the addition of an algae-based vegetable-like oil to add polyunsaturated fatty acids. How rations are chosen and developed is based on acceptance, nutrition, wholesomeness, producibility, cost, and sanitation. Additional requirements for rations include having a minimum shelf life of three years, being deliverable by air, being consumable in worldwide environments, and providing a complete nutritional profile. The new T-rations have been improved upon by increasing acceptable items and provide high quality meals while in the field. Freeze-dried coffee was also incorporated by replacing spray-dried coffee in the meal, ready-to-eat category. ==Stages ==
Stages
, the boundary between gas and liquid runs from the triple point to the critical point. Freeze-drying (blue arrow) brings the system around the triple point, avoiding the direct liquid–gas transition seen in ordinary drying (green arrow). There are four stages in the complete freeze drying process: pretreatment, freezing, primary drying, and secondary drying. Pretreatment Pretreatment includes any method of treating the product prior to freezing. This may include concentrating the product, formulation revision (i.e., addition of components to increase stability, preserve appearance, and/or improve processing), decreasing a high-vapor-pressure solvent, or increasing the surface area. Food pieces are often IQF treated to make them free flowing prior to freeze drying. Freeze dried pharmaceutical products are in most cases parenterals administered after reconstitution by injection which need to be sterile as well as free of impurity particles. Pre-treatment in these cases consists of solution preparation followed by a multi-step filtration. Afterwards the liquid is filled under sterile conditions into the final containers which in production scale freeze dryers are loaded automatically to the shelves. In many instances the decision to pretreat a product is based on theoretical knowledge of freeze-drying and its requirements, or is demanded by cycle time or product quality considerations. Freezing and annealing During the freezing stage, the material is cooled below its triple point, the temperature at which the solid, liquid, and gas phases of the material can coexist. This ensures that sublimation rather than melting will occur in the following steps. To facilitate faster and more efficient freeze drying, larger ice crystals are preferable. The large ice crystals form a network within the product which promotes faster removal of water vapor during sublimation. Amorphous materials do not have a eutectic point, but they do have a critical point, below which the product must be maintained to prevent melt-back or collapse during primary and secondary drying. Structurally sensitive goods In the case of goods where preservation of structure is required, like food or objects with formerly-living cells, large ice crystals break the cell walls, resulting in increasingly poor texture and loss of nutrients. In this case, rapidly freezing the material to below its eutectic point avoids the formation of large ice crystals. Usually, the freezing temperatures are between and . Primary drying During the primary drying phase, the pressure is lowered (to the range of a few millibars), and enough heat is supplied to the material for the ice to sublimate. The amount of heat necessary can be calculated using the sublimating molecules' latent heat of sublimation. In this initial drying phase, about 95% of the water in the material is sublimated. This phase may be slow (can be several days in the industry), because, if too much heat is added, the material's structure could be altered. In this phase, pressure is controlled through the application of partial vacuum. The vacuum speeds up the sublimation, making it useful as a deliberate drying process. Furthermore, a cold condenser chamber and/or condenser plates provide a surface(s) for the water vapor to re-liquify and solidify on. It is important to note that, in this range of pressure, the heat is brought mainly by conduction or radiation; the convection effect is negligible, due to the low air density. Secondary drying The secondary drying phase aims to remove unfrozen water molecules, since the ice was removed in the primary drying phase. This part of the freeze-drying process is governed by the material's adsorption isotherms. In this phase, the temperature is raised higher than in the primary drying phase, and can even be above , to break any physico-chemical interactions that have formed between the water molecules and the frozen material. Usually the pressure is also lowered in this stage to encourage desorption (typically in the range of microbars, or fractions of a pascal). However, there are products that benefit from increased pressure as well. After the freeze-drying process is complete, the vacuum is usually broken with an inert gas, such as nitrogen, before the material is sealed. At the end of the operation, the final residual water content in the product is extremely low, around 1–4%. == Applications ==
Applications
Freeze-drying causes less damage to the substance than other dehydration methods using higher temperatures. Nutrient factors that are sensitive to heat are lost less in the process as compared to the processes incorporating heat treatment for drying purposes. biologics, and other injectables. By removing the water from the material and sealing the material in a glass vial, the material can be easily stored, shipped, and later reconstituted to its original form for injection. Another example from the pharmaceutical industry is the use of freeze drying to produce tablets or wafers, the advantage of which is less excipient as well as a rapidly absorbed and easily administered dosage form. Freeze-dried pharmaceutical products are produced as lyophilized powders for reconstitution in vials, and more recently in prefilled syringes for self-administration by a person. Examples of lyophilized pharmaceutical drugs include: • Vancomycin, an intravenous antibiotic for treatment of complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis. • Activase, an intravenous "blood clot buster" used for treatment of ischemic stroke. • Carmustine, a chemotherapy drug used for treatment of glioblastoma, brainstem glioma, and other brain tumors. Biological products Examples of lyophilized biological products include: • Many vaccines such as live measles virus vaccine, typhoid vaccine, and meningococcal polysaccharide vaccine groups A and C combined. • This also include antibodies, some of which are blockbuster drugs: etanercept (Enbrel by Amgen), infliximab (Remicade by Janssen Biotech), rituximab, and trastuzumab (Herceptin by Genentech). • Cell extracts that support cell-free biotechnology applications such as point-of-care diagnostics and biomanufacturing are also freeze-dried to improve stability under room temperature storage. Lyophilized biologics can be pressed into pellets and tablets for anhydrous and high-density, solid-state storage of biological products. In bioseparations, freeze-drying can be used also as a late-stage purification procedure, because it can effectively remove solvents. Furthermore, it is capable of concentrating substances with low molecular weights that are too small to be removed by a filtration membrane. Freeze-drying is a relatively expensive process. The equipment is about three times as expensive as the equipment used for other separation processes, and the high energy demands lead to high energy costs. Furthermore, freeze-drying also has a long process time, because the addition of too much heat to the material can cause melting or structural deformations. Therefore, freeze-drying is often reserved for materials that are heat-sensitive, such as proteins, enzymes, microorganisms, and blood plasma. The low operating temperature of the process leads to minimal damage of these heat-sensitive products. Live material Some live cell cultures can be freeze-dried, stored for an extended period, and then reconstituted into a live, functional state. An excipient, more specifically a cryoprotectant, may be required. • Prokaryotes and yeast are relatively easy to freeze-dry and then resuscitate. • Live vaccines (described above) are also examples of this class. • The simpler blood cells (red blood cells and platelets) have been freeze-dried. With the right protection, recovery rates are as high as 90%. Even if the cell is damaged beyond resuscitation, it is preserved. This can be helpful for later research too: although the type strain culture for Vampirovibrio chlorellavorus could not been resuscitated, it contained enough DNA for its genome to be sequenced. Technological industry In chemical synthesis, products are often freeze-dried to make them more stable, or easier to dissolve in water for subsequent use. In nanotechnology, freeze-drying is used for nanotube purification to avoid aggregation due to capillary forces during regular thermal vaporization drying. Food bars , melon, meatball soup, tarator The primary purpose of freeze drying within the food industry is to extend the shelf-life of the food while maintaining the quality. It can also preserve raw ingredients such as egg whites for baking. NASA and military rations Because of its light weight per volume of reconstituted food, freeze-dried products are popular and convenient for hikers, as military rations, or astronaut meals. An instant coffee can be produced by freeze-drying a water extract of roasted beans. Insects Freeze-drying is used extensively to preserve insects for the purposes of consumption. Whole freeze-dried insects are sold as exotic pet food, bird feed, fish bait, and increasingly for human consumption. Powdered freeze-dried insects are used as a protein base in animal feeds, and in some markets, as a nutritional supplement for human use. Freeze-drying is also used as a means to memorialize pets after death. Rather than opting for a traditional skin mount when choosing to preserve their pet via taxidermy, many owners opt for freeze-drying because it is less invasive upon the pet's body. Other uses Organizations such as the Document Conservation Laboratory at the United States National Archives and Records Administration (NARA) have done studies on freeze-drying as a recovery method of water-damaged books and documents. While recovery is possible, restoration quality depends on the material of the documents. If a document is made of a variety of materials, which have different absorption properties, expansion will occur at a non-uniform rate, which could lead to deformations. Water can also cause mold to grow or make inks bleed. In these cases, freeze-drying may not be an effective restoration method. Advanced ceramics processes sometimes use freeze-drying to create a formable powder from a sprayed slurry mist. Freeze-drying creates softer particles with a more homogeneous chemical composition than traditional hot spray drying, but it is also more expensive. == Advantages ==
Advantages
Freeze-drying is viewed as the optimal method of choice for dehydration of food because of the preservation of quality, meaning characteristics of the food product such as aroma, rehydration, and bioactivity, are noticeably higher compared to foods dried using other techniques. Shelf-life extension Shelf-life extension results from low processing temperatures in conjunction with rapid transition of water through sublimation. With these processing conditions, deterioration reactions, including nonenzymic browning, enzymatic browning, and protein denaturation, are minimized. When the product is successfully dried, packaged properly, and placed in ideal storage conditions the foods have a shelf life of greater than 12 months. Re-hydration If a dried product cannot be easily or fully re-hydrated, it is considered to be of lower quality. Because if the final freeze dried product is porous, complete re-hydration can occur in the food. This signifies greater quality of the product and makes it ideal for ready-to-eat instant meals. Effect on nutrients and sensory quality Due to the low processing temperatures and the minimization of deterioration reactions, nutrients are retained and color is maintained. Freeze-dried fruit maintains its original shape and has a characteristic soft crispy texture. == Disadvantages ==
Disadvantages
Microbial growth Since the main method of microbial decontamination for freeze drying is the low temperature dehydration process, spoilage organisms and pathogens resistant to these conditions can remain in the product. Although microbial growth is inhibited by the low moisture conditions, it can still survive in the food product. An example of this is a viral hepatitis A outbreak that occurred in the United States in 2016, associated with frozen strawberries. If the product is not properly packaged and/or stored, the product can absorb moisture, allowing the once inhibited pathogens to begin reproducing as well. ==Equipment and types of freeze dryers==
Equipment and types of freeze dryers
There are many types of freeze-dryers available, however, they usually contain a few essential components. These are a vacuum chamber, The freeze-dryer can run for a few hours or days depending on the product. Contact freeze dryers Contact freeze dryers use contact (conduction) of the food with the heating element to supply the sublimation energy. This type of freeze dryer is a basic model that is simple to set up for sample analysis. One of the major ways contact freeze dryers heat is with shelf-like platforms contacting the samples. The shelves play a major role as they behave like heat exchangers at different times of the freeze-drying process. They are connected to a silicone oil system that will remove heat energy during freezing and provide energy during drying times. Additionally, the shelf-fluid system works to provide specific temperatures to the shelves during drying by pumping a fluid (usually silicone oil) at low pressure. The downside to this type of freeze dryer is that the heat is only transferred from the heating element to the side of the sample immediately touching the heater. This problem can be minimized by maximizing the surface area of the sample touching the heating element by using a ribbed tray, slightly compressing the sample between two solid heated plates above and below, or compressing with a heated mesh from above and below. Radiant freeze dryers Radiant freeze dryers use infrared radiation to heat the sample in the tray. This type of heating allows for simple flat trays to be used as an infrared source can be located above the flat trays to radiate downwards onto the product. Infrared radiation heating allows for a uniform heating of the surface of the product, but has little capacity for penetration so it is used mostly with shallow trays and homogeneous sample matrices. Microwave-assisted freeze dryers Microwave-assisted freeze dryers utilize microwaves to allow for deeper penetration into the sample to expedite the sublimation and heating processes in freeze-drying. This method can be complicated to set up and run as the microwaves can create an electrical field capable of causing gases in the sample chamber to become plasma. This plasma could potentially burn the sample, so maintaining a microwave strength appropriate for the vacuum levels is imperative. The rate of sublimation in a product can affect the microwave impedance, in which power of the microwave must be changed accordingly. ==See also==
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