Organ-on-chip research : Mechanically tuned lung-on-a-chip model (MECH-LoC project)
Chronic obstructive pulmonary diseases (COPD), like emphysema or chronic bronchitis, affect about 10% of the population, reducing the quality of life of affected patients.
To better understand these disorders and to screen potentially efficient drugs, appropriate lung models need to be developed. The current models, based on 2D cell culture or living animal studies, are however quite limited in physiological relevance. Advances in microfluidics, and in particular with organ-on-chip, offer a powerful alternative to study the lung membrane, providing a more realistic 3D cell culture environment and the potential to reduce the number of animal studies.
State of the art lung-on-chip systems model the lung using two chambers, one filled with air and the other with liquid, separated by a semi-permeable membrane, typically a thin layer of flexible polymer such as polydimethylsiloxane (PDMS). Cells are seeded on each side of this membrane to reproduce the liquid/air interface. Flanking vacuum chambers allow the membrane to be cyclically inflated to replicate breathing. This kind of lung-on-chip system is suitable for measuring gas exchange, metabolite concentrations, or to screen new drugs.
Lung-on-a-chip microfluidic device: Application of vacuum in the side channels stretches the membrane separating the air and liquid chambers.
Lungs are constantly undergoing mechanical stress during breathing, making the elasticity of the membrane a crucial parameter for understanding lung diseases. However, the polymer typically used to mimic the air / liquid membrane has an elastic modulus of up to one thousand times higher than its physiological equivalent and does not offer biological stimuli. To advance lung-on-a-chip models, the aim of this project is to control the mechanical properties of the membrane by adding fibrous matrix proteins (e.g. collagen and elastin). The fast and stable microfluidic flow control system developed by Elveflow will help to finely control membrane deformation and culture media. The mechanical properties of this model lung membrane can be thus adapted to different disease phenotypes to be as relevant as possible in the development and screening of treatments.
As an alternative to conventional organ-on-chip materials such as PDMS, we also intend to use FlexdymTM polymer to make our lung-on-a-chip devices, a fully biocompatible material which makes possible the integration of cells into the system prior to chip assembly.
Dr. Lisa Muiznieks
- Post-Doc at Hospital for Sick Children (Canada), working on elastin structure and function
- PhD in Biochemistry (Sydney University, Australia)
- Bachelor of Science in Molecular Biology and Genetics (Sydney University, Australia)
AREAS OF EXPERTISE: Structural biology, Protein elasticity, Lung-on-chip, Air-liquid interface