When using a freeze dryer for process design or optimization, the first thing to do is to measure several key temperatures of the sample, so that we can design a freeze drying curve based on these temperatures.

What methods should be used to measure those key temperatures? Today we will discuss it.

　1. Measurement method for eutectic point temperature (eutectic point temperature)

The measurement of eutectic point temperature can be carried out using methods such as resistance measurement, capacitance measurement, differential scanning calorimetry, direct observation under low-temperature microscope, and numerical formula calculation. Each method has its own advantages and disadvantages.

(1) Conductivity or resistance measurement method

The conductivity (resistance) method for measuring eutectic points is simple and convenient to operate, and is currently the most widely used. However, it cannot accurately determine non electrolyte solutions.

It is impossible to determine whether a sample is frozen by observing its appearance during the pre freezing process. By measuring the changes in conductivity when the product structure changes during the freezing process, it can be determined whether the freezing is complete.

Principle: According to the ionization theory of S.A. Arrhenius, when impurities are present in water, some of them decompose into electrical ions. At this point, water becomes conductive, and as the temperature decreases, the resistance of the solution gradually increases. When the solution solidifies into a solid, the ions in the solution lose their ability to move freely, and the resistance suddenly increases. At this point, the temperature is the eutectic point; On the contrary, the temperature at which the resistance of frozen products suddenly decreases during the heating process is the melting point.

The in-situ silicone oil freeze-drying machine from Beijing Fourth Ring Road can be equipped with a eutectic point tester, which uses resistance measurement method to determine the eutectic point temperature of the sample.

(2) Capacitance measurement method

Principle: During the freezing and heating process of the sample, the capacitance will undergo significant changes due to the crystallization and melting of moisture. This property can be used to determine the eutectic point and detect whether the product is frozen, or to set an appropriate capacitance value to directly control heating sublimation.

The dielectric constants of water and ice are different, with water having a dielectric constant of 78.3 (at a water temperature of 25 ℃) and ice having a dielectric constant of 3-4. However, the dielectric constant of physically adsorbed and chemically bound water varies between 10 and 80 depending on the degree of binding. A capacitor is composed of two metal electrodes separated by an insulator, and the sample solution is placed between the electrodes as a dielectric. During the freeze-drying process, the capacitance of the capacitor will change to varying degrees. During the sublimation process, as the ice crystals gradually decrease, the capacitance also decreases. Therefore, the slope of the change in capacitance over time reflects the rate of mass transfer. Therefore, in reality, the capacitance change curve is the drying curve of the ice crystals. In addition, the performance of dielectrics varies very little between vacuum and air, and the determination of dielectric constant can be considered independent of pressure. Therefore, the capacitance method can be directly applied in the freeze-drying process.

The capacitance measurement method has a wider range of applications than the resistance measurement method, and can be used for electrolyte and non electrolyte solutions, as well as for granular or non-uniform block materials.

(3) Thermal analysis method

Differential Scanning Calorimetry (DSC) is a method of measuring the energy difference between a sample and a reference substance as a function of temperature, under the control of a temperature program (heating or cooling). DSC can accurately and quickly calculate the heat absorption and release (enthalpy) and characteristic temperature (starting point, peak value, termination point, etc.) of thermal effects.

The DSC measurement method is currently a commonly used method for measuring eutectic points and melting points in fields such as medicine, inorganic materials, metal materials, composite materials, rubber, fibers, coatings, adhesives, biological organisms, and food.

In addition to the three commonly used methods mentioned above, the eutectic (melting) point of the solution can also be obtained by direct observation under a low-temperature microscope or calculation using numerical formulas.

　　2. Measurement method for glass transition temperature

The commonly used method for measuring the glass transition temperature of a sample is the DSC method. Due to the fact that the glass transition temperature is the temperature at which a substance transitions from a highly fluid liquid state to a highly viscous and poorly fluid glass transition state. Therefore, using DSC method to record the energy difference between the sample and the reference substance, the specific heat change on the DSC spectrum is the glass transition temperature of the sample.

In the absence of thermal effects in the sample, the signal difference between the reference end and the sample end is close to 0. On the DSC spectrum, this is reflected as a nearly horizontal line, known as the "baseline". Once a thermal effect occurs in the sample, there will be a temperature difference/heat flux signal difference between the sample end and the reference end. According to DIN standards and thermodynamic regulations, positive values represent the endothermic peak of the sample, and typical endothermic effects include melting, decomposition, desorption, etc; Negative values represent exothermic peaks, and typical exothermic effects include crystallization, oxidation, solidification, etc; The change in specific heat is reflected in the variation of baseline height, that is, the step like inflection on the curve, and the glass transition is a typical change in specific heat.

In addition, differential thermal analysis (DTA) method and low-temperature microscope direct observation method can also be used for measurement.

△ Beijing Fourth Ring Road departure freeze-drying machine freeze-drying samples

　　3. Measurement method for disintegration temperature

Before designing the freeze-drying process, measuring the disintegration temperature of the sample is an important step in process design and optimization. The current mainstream method for measuring disintegration temperature is the direct observation method using a low-temperature microscope.

The direct observation method of low-temperature microscope is to observe the crystallization process of the product using a low-temperature microscope, and obtain the eutectic point (eutectic point) temperature, collapse temperature, and glass transition temperature based on the captured images or videos.

Before freeze-drying the sample, the key temperatures of the sample must be measured first in order to design a more efficient and reasonable freeze-drying curve. Of course, having a high-performance freeze-drying machine will also make it easier to control the entire freeze-drying process of the sample.