Reflection Microscope for characterization of collective mucociliary activity
Primary ciliary dyskinesia (PCD) is a rare hereditary disease impairing the ciliary activity and resulting in a variety of respiratory symptoms, such as neonatal respiratory distress in term-born infants, chronic rhino-sinusitis and persistent wet cough from the day of birth, and recurrent respiratory tract infections often resulting in later bronchiectasis. Mutations in more than 50 genes are known to cause defects in the structure and function of cilia. Abnormalities in the ciliary structure lead to ciliary dyskinesia, which results in an impairment of the mucociliary transport. Reduced mucociliary transport then leads to less efficient removal of respiratory pathogens from the airways. Due to the high number of potentially involved genes, the diagnosis of PCD is very challenging. There is no single gold standard test and a combination of methods has to be performed. Therefore, we would like to use computational high-speed video reflection microscopy (CRM) to assess the collective mucociliary activity in air-liquid interface (ALI) cell cultures of nasal epithelial cells derived from patients with suspicion of PCD. This approach has the potential to become the first diagnostic approach allowing to diagnose PCD in a highly accurate as well as automated and cost-effective way.
With the support of the Berne University Research Foundation we bought a reflection microscope to record the surface of ALI-cultured, differentiated cells of patients suspicious for PCD. The addition of a climate chamber furthermore enabled temperature control during experiments. The videos can be analyzed using our Cilialyzer software and we will investigate which parameters of the collective ciliary activity could discriminate reliably and sensitively between healthy and PCD. Furthermore, the microscope is used to test the potential of various drugs (e.g. cystic fibrosis modulator drugs) to improve ciliary activity and mucociliary transport in vitro.
PD Dr. Loretta Müller
Department for BioMedical Research, Lung Precision Medicine (LPM)
Pädiatrische Pulmonologie, Inselspital, Kinderklinik


Figure 1: Reflection microscopy partially funded by the Berne University Research Foundation additionally equipped with a climate chamber to regulate the temperature (mostly kept to 37°C).
Figure 2: Image example of a video taken with the reflection microscope of a healthy ALI cultured cell culture.