Freeze drying (also known as lyophilization) is a water removal process typically used to preserve perishable materials, with the goal of extending their shelf life and/or preparing them for transport. Freeze drying works by freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to change directly to a vapor (sublimate).

冷凍干燥（也稱為凍干）是一種除水工藝，通常用于保存易變質(zhì)的物質(zhì)比如藥品，疫苗，檢測試劑等，目的是延長其保質(zhì)期和/或?yàn)檫\(yùn)輸做好準(zhǔn)備。冷凍干燥的工作原理是冷凍材料，然后降低壓力并增加熱量，使材料中的冷凍水直接變成蒸汽（升華）。

How does Freeze Drying work?

冷凍干燥是如何工作的？

Freeze drying occurs in three phases:

冷凍干燥分為三個(gè)階段：

Freezing

預(yù)凍

Primary Drying (Sublimation)

主要干燥（升華）

Secondary Drying (Adsorption)

二次干燥（解析干燥）

Proper freeze drying can improve the efficiency or failure of freeze drying.

合理的工藝可以讓凍干效率大大提高和凍干失敗

Freezing Phase

預(yù)凍階段

Freezing is the most critical phase of freeze drying, and there are many methods for it. Freezing can be done in a freezer, a chilled bath (shell freezer) or on a shelf in the freeze dryer. Cooling the material below its triple point ensures that sublimation, rather than melting, will occur. This preserves its physical form.

預(yù)凍是冷凍干燥最關(guān)鍵的階段，有很多方法可以做到這一點(diǎn)。預(yù)凍可以在冷凍室、預(yù)凍浴或冷凍干燥機(jī)的架子上進(jìn)行。將材料冷卻到其三相點(diǎn)以下可確保發(fā)生升華，而不是熔化。這保留了產(chǎn)品的結(jié)構(gòu)。

Freeze drying is easiest to accomplish using large ice crystals, which can be produced by slow freezing or annealing. However, with biological materials, when crystals are too large they may break the cell walls, and that leads to less-than-ideal freeze drying results. To prevent this, the freezing is done rapidly. For materials that tend to precipitate, annealing can be used. This process involves fast freezing, then raising the product temperature to allow the crystals to grow.

冷凍干燥最容易通過使用大冰晶來實(shí)現(xiàn)，這可以通過緩慢冷凍或退火來產(chǎn)生。然而，對于生物材料，當(dāng)晶體過大時(shí)可能會(huì)破壞細(xì)胞壁，導(dǎo)致冷凍干燥結(jié)果不理想。為了防止這種情況發(fā)生，冷凍過程需要迅速完成。

對于容易沉淀的材料，可以使用退火。這個(gè)過程涉及快速冷凍，然后提高產(chǎn)品溫度以允許晶體生長。

Primary Drying (Sublimation) Phase

主干燥（升華）階段

Freeze drying’s second phase is primary drying (sublimation), in which the pressure is lowered and heat is added to the material in order for the water to sublimate. The vacuum speeds sublimation. The cold condenser provides a surface for the water vapor to adhere and solidify. The condenser also protects the vacuum pump from the water vapor. About 95% of the water in the material is removed in this phase. Primary drying can be a slow process. Too much heat can alter the structure of the material.

冷凍干燥的第二階段是主干燥（升華），其中降低壓力并向材料中添加熱量以使水升華。真空加速升華。冷凝器（冷阱）為水蒸氣的粘附和凝固提供了一個(gè)表面。冷凝器還可以保護(hù)真空泵免受水蒸氣的影響。在這個(gè)階段，材料中大約95%的水被去除。主干燥可能是一個(gè)緩慢的過程。過多的熱量會(huì)改變產(chǎn)品的結(jié)構(gòu).

Secondary Drying (Adsorption) Phase二次干燥（解析）階段

Freeze drying’s final phase is secondary drying (adsorption), during which the ionically-bound water molecules are removed. By raising the temperature higher than in the primary drying phase, the bonds are broken between the material and the water molecules. Freeze dried materials retain a porous structure. After the freeze drying process is complete, the vacuum can be broken with an inert gas before the material is sealed. Most materials can be dried to 1-5% residual moisture.

冷凍干燥的最后階段是二次干燥（解析），在此期間，離子結(jié)合的水分子被去除。通過將溫度提高到高于初級干燥階段的溫度，材料和水分子之間的鍵被破壞。凍干材料保持多孔結(jié)構(gòu)。冷凍干燥過程完成后，在材料密封之前，可以用惰性氣體打破真空。大多數(shù)材料可以干燥至1-5%的殘留水分。

Problems To Avoid During Freeze Drying

冷凍干燥過程中應(yīng)避免的問題

Heating the product too high in temperature can cause melt-back or product collapse

將產(chǎn)品加熱溫度過高會(huì)導(dǎo)致熔化或產(chǎn)品塌陷

Condenser overload caused by too much vapor hitting the condenser.

過多的蒸汽撞擊冷凝器導(dǎo)致的冷凝器過載.

Too much vapor creation

產(chǎn)生過多的蒸汽

Too small a condenser area

冷凝器面積太小

Insufficient refrigeration

/制冷不足

Vapor choking – the vapor is produced at a rate faster than it can get through the vapor port, the port between the product chamber and the condenser, creating an increase in chamber pressure.

蒸汽窒息 – 蒸汽的產(chǎn)生速度快于通過蒸汽口（產(chǎn)品腔室和冷凝器之間的端口）的速度，從而增加腔室壓力。

Crystalline結(jié)晶

The material forms crystals when frozen.該材料在冷凍時(shí)形成晶體。

Has a eutectic point or multiple eutectic points具有一個(gè)或多個(gè)共晶點(diǎn)

Fast freezing creates small crystals which are hard to dry

快速冷凍會(huì)產(chǎn)生難以干燥的小晶體

Annealing can help form bigger crystals

退火可以幫助形成更大的晶體

Amorphous 無晶體形態(tài)

Multi-component mixtures which do not crystallize and do not have a eutectic point. They turn into a ‘glass.’

不結(jié)晶且沒有共晶點(diǎn)的多組分混合物。它們變成了一個(gè)"玻璃態(tài)"。 

Does not have a eutectic point沒有共晶點(diǎn)

For amorphous materials, freeze drying needs to be performed below the glass transition temperature

對于非晶態(tài)材料，需要在低于玻璃化轉(zhuǎn)變溫度的情況下進(jìn)行冷凍干燥。

collapse塌陷

The point at which the product softens to the extent that it can no longer support its own structure. This can be a problem for many reasons:

產(chǎn)品軟化到無法再支撐其自身結(jié)構(gòu)的程度。這可能是一個(gè)問題，原因有很多：

Loss of physical structure物理結(jié)構(gòu)喪失

Incomplete drying干燥不完全

Decreased solubility溶解度降低

Lots of ablation (splat)大量消融（飛濺）

Critical Temperature臨界溫度

During freeze drying, the maximum temperature of the product before its quality degrades by melt-back or collapse.

在冷凍干燥過程中，產(chǎn)品質(zhì)量因熔化或塌陷而下降之前的最高溫度。