Acellular microfluidic lung on a chip design for gas exchange Introduction Design Methods Conclusions Acknowledgements Mathematical Analysis Integration Experiments Results Validation Experiments Gillie Agmon 1, Shashank Anand 1, Arjun Bhungal 1, Ben Yang 1, Max Yang 1, Josh Yang 1, Han Liang Lim 1, Aereas Aung 1, Roger Chiu 2, Dr. Yuhwa Lo 3, Dr. Shyni Varghese 1 1 Department of Bioengineering; UC San Diego; 2 Department of Material Science; UC San Diego; 3 Department of Electrical and Computer Engineering; UC San Diego In vivo testing currently faces two major challenges: time and money. Pushing a drug through animal and clinical testing for efficacy and safety can easily be bogged down by ethical considerations and cost drug companies millions of dollars, ultimately increasing the market price of the drug. PDMS-based microfluidic ‘lab-on-a-chip’ devices provide a few advantages. Future Directions 1.Fast fabrication 2.Small working volumes 3.Laminar flow allows for easy mass transport models. 4.PDMS is gas-permeable Our project seeks to work toward an affordable and modular ‘human-on-a-chip’ device that can provide a view of the systemic effects of the drug without the need of live test subjects thus eliminating the major drawbacks of time and money. This poster focuses on the fabrication and testing of an acellular microfluidic diffusive gas exchange system that aims to emulate a human lung. Materne 2013 The design is made of three components to efficiently conduct oxygen and carbon dioxide exchange from the liquid. Below are the CAD images. Serpentine liquid channels – Thin flat membrane – Wide Air Channels This representative schematic shows the fabrication of the design. (A-C) Photolithography is used to create a negative of the final PDMS structure using and photomask. (D) PDMS is poured over the mold and then cured, resulting in a the desired channels. Two structures will be created and separated by a thin spin coated PDMS membrane as shown in (E) to create the air channels above the liquid channels. (F) Shows the final structure. Images are not to scale. First PrototypeLeaking PrototypeSuccessful Prototype Leak Testing Prototype Dye Calibration and Testing Determine oxygen exchange dependence on oxygen concentration, a possible challenge for integration into cellular systems Optimize gas diffusivity across the membrane by thinning the membrane or slowing the flow rate Determine capacity for CO 2 exchange from fluid into air Determine capacity for aerosolized drug distribution through chip Begin development of other components such as acellular kidney (excretion), cellular liver (media detoxification) and heart (perfusion pump) Implement endothelial cells throughout chip that can secrete factors such as Angiotensin Converting Enzyme Integrate lung-on-a-chip with other components to observe systemic behavior Explore possible applications in gas exchange for micro-bioreactors Membrane AIR FLUID O2O2 O2O2 O2O2 O2O2 O2O2 O2O2 CO 2 This graph shows that the flow rate has an effect on oxygen diffusion. According to this model a flow rate slower than 10 cm/sec is unnecessary References The successful fabrication of the prototype and the mathematical modeling of the oxygen diffusion provides the confidence that this design will successfully complete the necessary gas diffusion required to sustain cellular components of an integrated human-on-a-chip system This system will provide a platform for simplified and more accurate drug testing as well as a way to create diseased models for scientific inquiries