Freeze drying

# Overview
Freeze drying (also known as lyophilization or cryodessication) is a dehydration process typically used to preserve a perishable material or make the material more convenient for transport. Freeze drying works by freezing the material and then reducing the surrounding pressure and adding enough heat to allow the frozen water in the material to sublime directly from the solid phase to gas.

# Freeze drying protectants
Similar to cryoprotectants, some molecules protect freeze dried material. Known as lyoprotectants, these molecules are typically polyhydroxy compounds such as sugars (mono-, di-, and polysaccharides), polyalcohols, and their derivatives. Trehalose and sucrose are natural lyoprotectants. Trehalose is produced by a variety of plant, fungi, and invertebrate animals that remain in a state of suspended animation during periods of drought (also known as anhydrobiosis).

# The freeze-drying process
There are three stages in the complete freeze-drying process: freezing, primary drying, and secondary drying.

## Freezing
The freezing process consists of freezing the material. In a lab, this is often done by placing the material in a freeze-drying flask and rotating the flask in a bath, called a shell freezer, which is cooled by mechanical refrigeration, dry ice and methanol, or liquid nitrogen. On a larger-scale, freezing is usually done using a freeze-drying machine. In this step, it is important to cool the material below its eutectic point, the lowest temperature at which the solid and liquid phase of the material can coexist.  This ensures that sublimation rather than melting will occur in the following steps. Larger crystals are easier to freeze dry. To produce larger crystals the product should be frozen slowly or can be cycled up and down in temperature. This cycling process is called annealing.  However, in the case of food, or objects with formerly living cells, large ice crystals will break the cell walls.  As discovered by Clarence Birdseye, when food is frozen at 40 C to 45 C or below, then it tastes better.  Usually, the freezing temperatures are between 50 C and 80 C. The freezing phase is the most critical in the whole freeze drying process, because the product can be spoiled if badly done.
Amorphous (glassy) materials do not have a eutectic point, but do have a critical point, below which the product must be maintained to prevent melt-back or collapse during primary and secondary drying.
Large objects take a few months to freeze dry.

## 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 water 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 materials structure could be altered.
In this phase, pressure is controlled through the application of partial vacuum. The vacuum speeds 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 vapour to re-solidify on. This condenser plays no role in keeping the material frozen; rather, it prevents water vapor from reaching the vacuum pump, which could degrade the pump's performance. Condenser temperatures are typically below 50 C (60 F).
It's important to note that in this range of pressure, the heat is mainly brought by conduction or radiation, the convection effect can be considered as insignificant.

## Secondary drying
The secondary drying phase aims to sublimate the water molecules that are adsorbed during the freezing process, since the mobile water molecules were sublimated in the primary drying phase. This part of the freeze-drying process is governed by the materials adsorption isotherms. In this phase, the temperature is raised higher than in the primary drying phase, and can even be above 0 C, 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 sublimation (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 humidity in the product is around 1% to 4%, which is extremely low.

# Properties of freeze-dried products
If a freeze-dried substance is sealed to prevent the reabsorption of moisture, the substance may be stored at room temperature without refrigeration, and be protected against spoilage for many years. Preservation is possible because the greatly reduced water content inhibits the action of microorganisms and enzymes that would normally spoil or degrade the substance.
Freeze drying also causes less damage to the substance than other dehydration methods using higher temperatures. Freeze drying does not usually cause shrinkage or toughening of the material being dried. In addition, flavours and smells generally remain unchanged, making the process popular for preserving food. Unfortunately, water is not the only chemical capable of sublimation and the loss of other volatile compounds such as acetic acid (responsible for the smell of vinegar) and alcohols can yield undesirable results.
Freeze-dried products can be rehydrated (reconstituted) much more quickly and easily because the process leaves microscopic pores. The pores are created by the ice crystals that sublimate, leaving gaps or pores in its place. This is especially important when it comes to pharmaceutical uses. Lyophilization can also be used to increase the shelf life of some pharmaceuticals for many years.

# Applications of freeze-drying

## Pharmaceutical and biotechnology
Pharmaceutical companies often use freeze drying to increase the shelf life of products, such as vaccines and other injectables. By removing the water from the material and sealing the material in a vial, the material can be easily stored, shipped and later reconstituted to its original form for injection. freeze drying increase the stability of  product. And some products unstable in liquid form so lyophilization is benefical technique

## Food industry
Freeze drying is used to preserve food and make it very lightweight.  The process has been popularized in the forms of freeze-dried ice cream, an example of astronaut food. It is also popular and convenient for hikers because the reduced weight allows them to carry more food and reconstitute it with available water. Instant coffee is sometimes freeze dried, despite high costs of freeze dryers. The coffee is often dried by vaporization in a hot air flow, or by projection on hot metallic plates. Freeze dried fruit is used in some breakfast cereal. However, the freeze-drying process is used more commonly in the pharmaceutical industry.  Military forces may use freeze dried food, known as Meal, Ready-to-Eat (MRE).  The meals are typically prepared simply by adding hot water, which rehydrates and reconstitutes the food and may also cook it slightly.

## Technological industry
In chemical synthesis, products are often lyophilized to make them more stable, or easier to dissolve in water for subsequent use.
In bioseparations, freeze drying can also be used 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.

## Other uses
Recently, some taxidermists have begun using freeze drying to preserve animals, such as pets.
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 homogenous chemical composition than traditional hot spray drying, but it is also more expensive.
In high altitude environments, the low temperatures and pressures can sometimes produce natural mummies by a process of freeze-drying.

# Freeze-drying equipment
There are essentially three categories of freeze dryers: rotary evaporators, manifold freeze dryers, and tray freeze dryers.
Rotary freeze dryers are usually used with liquid products, such as pharmaceutical solutions and tissue extracts.
Manifold freeze dryers are usually used when drying a large amount of small containers and the product will be used in a short period of time. A manifold dryer will dry the product to less than 5% moisture content. Without heat only primary drying (removal of the unbound water) can be achieved. A heater needs to be added for secondary drying, which will remove the bound water and will produce a lower moisture content.
Tray freeze dryers are more sophisticated and are used to dry a variety of materials. A tray freeze dryer is used to produce the driest product for long-term storage. A tray freeze dryer allows the product to be frozen in place and performs both primary (unbound water removal) and secondary (bound water removal) freeze drying, thus producing the driest possible end-product. Tray freeze dryers can dry product in bulk or in vials. When drying in vials, the freeze dryer is supplied with a stoppering mechanism that allows a stopper to be pressed into place sealing the vial before it is exposed to the atmosphere. This is used for long term storage, such as vaccines.