ABSTRACT

Many drug and toxicology tests cannot be performed directly on humans. Therefore, animal tests are routinely used to predict human patient responses; however, anatomical and physiological differences between animals and humans make it difcult to extrapolate results from animals to humans. Furthermore, for reasons of ethics and cost, as well as to better predict human, rather than animal, responses, there is an increasing interest in the construction of more physiological in vitro cell culture models. Recent advances in the eld of microuidics, which is the technology to manipulate small volumes of uid, have advanced lung-on-a-chip technology to address these needs. It is noted that lungs-on-a-chip are typically not models of the entire lung or devices made with the intent of performing gas exchange functions for animals or humans, but rather for

3.1 Introduction ............................................................................................................................ 57 3.2 Why Create Lungs-on-a-Chip? ............................................................................................... 58 3.3 Commonly Used Microfabrication Techniques ...................................................................... 59

3.3.1 Photolithography ......................................................................................................... 59 3.3.2 Soft Lithography ......................................................................................................... 59

3.4 Microuidic Models of the Small Airways ............................................................................60 3.4.1 Parallel-Plate Model ................................................................................................... 61

3.4.1.1 Device Construction .................................................................................... 61 3.4.1.2 Cell Culture .................................................................................................. 61 3.4.1.3 Air Fingers Generate Fluid Mechanical Stress ............................................ 61

3.4.2 Microchannel Model ................................................................................................... 61 3.4.2.1 Device Construction .................................................................................... 62 3.4.2.2 Cell Culture .................................................................................................. 62 3.4.2.3 Liquid Plug Propagation and Rupture Generates Fluid Mechanical

Stresses ................................................................................................................63 3.5 Microuidic Models of the Alveoli ........................................................................................64