Lab-on-a-Disc platform for cell culture in flow and drug testing

The process of developing and bringing into market new drugs represents one of the fundamental activities which improves human health and quality of life. The preclinical phase of the Drug Development Process is considered a crucial step for the discovery of new potential pharmaceutical compounds. In fact, at this stage, screening of new molecules and essential pre-tests are carried out using in vitro models. In this view, in vitro systems are valuable tools to understand cell mechanisms and the effects of drugs on a culture. A wide range of in vitro models have been created during the years, where the majority are based on static 2D cultures. Although traditional static cultures are still the most used in scientific research due to their simplicity, the need for better mimicking certain aspects of the in vivo microenvironment has led to the development of several new systems based on perfusion. Perfusion culture systems provide a continuous flow of nutrients and oxygen over the culture, which better reproduces the mechanisms found in a living organism. Among these systems, a key role is played by microfluidic devices, the so-called Lab-on-a-Chip (LoC). LoCs allow the integration of several operational units and lab protocols on a single chip where cells are grown using dynamic conditions over time. Despite their advantages, these systems still rely on expensive and complex pressure sources (e.g. pumps and tubing) and electronics. Centrifugal microfluidics, the so-called Lab-on-a-Disc (LoD), is a possible solution to these problems. Various operational units (e.g. valving and mixing) can be implemented on LoD platforms, allowing to reduce size, complexity, volumes required and costs of these systems. These in vitro systems are mainly used for sample pre-treatment, analysis and detection of a specific compound, biochemical markers, etc. While Lab-on-a-Disc platforms are largely used for biological assays (e.g. immune-assays), they are rarely employed for cell-based assays. In this thesis, a novel application of centrifugal microfluidics is presented. A compact and robust Lab-on-a-Disc device is used for long-term cell culture (up to 6 days) and drug testing. In particular, the LoD was used for culturing bacterial and mammal cells in two different applications. Once the cells were grown on the platform, different antibiotic treatments were tested on bacterial biofilm and cytotoxicity assays were carried out on mammalian cells where real time detection was also possible to achieve. The LoD platform provided relevant and reproducible results in both applications, proving to be a reliable tool. The results obtained make this device highly relevant in the initial phase of drug screening, representing a possible alternative to traditional cell culture systems and in vitro models.