Atomic Layer Deposition in PDMSMicrofluidic Chips forMedical Radionuclide Separation

Abstract

In the field of cancer diagnostics and targeted therapy, medical radionuclides have gained increasing interest. These nuclides usually have their own unique emission characteristics and reasonably short half-life, and when combined with antibodies/peptides can be used as radiopharmaceuticals. After injection into a patient, the radiopharmaceuticals then interact with specific proteins expressed in a cancer cell. As a result, precise imaging of the cancer cells and/or targeted delivery of therapeutic doses can be performed. Despite decades of research in medical radionuclides, only a handful manage to be authorized for clinical uses. While their clinical efficacy and safety are still parts of the ongoing research, many radionuclides are also difficult to produce since they are either too short in half-life, complicated to label or limited in availability. Consequently, efforts have been made to also advance the production of medical radionuclides, including the critical separation steps. When it comes to the separation steps, the processes must take place in a relatively short time with high efficiency and reliability. Among many technologies, (liquid-liquid) extraction in microfluidic devices holds the potential to accommodate this by offering a controlled environment with a high surface-to-volume ratio. The large contact area allows the radionuclides to be separated from their respective target materials, from one phase to the other in a fast, continuous and efficient manner. The commonly used material of choice to fabricate microfluidic chips is polydimethylsiloxane (PDMS). It is easy to replicate, suitable for rapid prototyping, resistant to extreme pH and transparent. Yet, PDMS suffers from being incompatible with organic solvents, commonly used as one of the phases in liquid-liquid extractions. Unfortunately, current solutions involving bulk-, ex-situ surface-, and in-situ liquid phase modifications are limited and practically demanding. To overcome PDMS’s main limitation, we develop a new method to deposit metal oxide nano-coatings on the walls of bonded microfluidic chips. These nano-coatings can offer protection without modifying the convenient PDMS bulk properties. Therefore, the central theme of this PhD dissertation is to develop a PDMS microfluidic technology with nano-coatings, able to separate medical radionuclides from their irradiated target materials through continuous flow liquid extraction. We started by depositing