Inert thermocouple with nanometric thickness for lyophilization monitoring

This paper describes the development and characterization of thermocouples with nanometric thickness made inert by means of a glass-like coating. These thermocouples are designed to follow the freeze-drying process of pharmaceutical products without perturbing freezing and drying steps but can be used in several other applications where the perturbation introduced by wire thermocouples can prevent a correct measurement to be performed. The developed thermocouples are T-type with a thickness in the range of 50–200 nm and are embedded into the vial wall owing to a SiO2-like coating with a glass-like structure and a thickness of 200 nm. This way, they actually measure the product temperature without altering thermal distribution and shape of the drying front and withoutmodifying the cake structure during the freezing step, so that the results can be extended to the other not instrumented vials. The SiO2-like coating ensures that no ion exchange takes place between thermocouple metals and lyophilized product, thus avoiding the risk of contamination and denaturation. The extremely low thickness requires a preliminary characterization of the thermocouples in order to determine their Seebeck coefficient, but the sealing provided by the coating, which prevents oxidization and degradation of the metallic strips, ensures that the obtained coefficients can be used for a long time.