Lung-On-A-Chip
Microfluidic lung-on-a-chip is a miniature experimental platform designed and fabricated based on microfluidic technology, which is used to simulate the structure and function of the lung. The microfluidic lung organ chip model simulates the trachea or alveoli and blood vessels through microfluidic channels and simulates the flow velocity of air in alveoli or fluid shear stress in blood vessels by controlling the flow rate of air or fluid. The accurate simulation of pulmonary physiological and pathological conditions shows significant potential in human lung physiology, disease etiology, toxicology, and drug screening.
Advantages of Lung-on-Chips
Microfluidic lung-on-a-chip has many advantages, such as high repeatability, high controllability, high simulation, easy operation, and automation. Compared with traditional cell culture and animal experiments, microfluidic lung-on-chips have greater accuracy and reliability and can better simulate the physiological and pathological conditions of the lung. Therefore, it can provide an efficient and reliable experimental platform for lung disease research, drug screening, and toxicity assessment. In addition, it is expected to become an important tool for lung disease treatment and drug development.
Principle of Lung-on-Chips
The main principle of lung-on-chips is to fabricate a specific shape of microstructure on microchips made of polydimethylsiloxane (PDMS), glass, polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS) or parchment, and various biomaterials. There are usually two microfluidic channels on the chip. The upper channel plants alveolar epithelial cells and provides oxygen to form a gas-liquid interface that simulates alveoli. Vascular endothelial cells were implanted in the lower channel and continuously perfused with a culture medium to simulate capillary channels and fluid shear stress, which were separated by porous membranes to simulate the alveolar septum. On both sides of the lung organ chip, there are side chambers connected to two vacuum pumps, which regularly change the pressure of the side chamber, cause regular stretching of the porous membrane, and simulate the respiratory movement of the lung. The cells will form functional tissue units after being cultured for a period of time.
Lung-on-a-Chip Experimental Method
- Design and fabrication of microfluidic lung-on-a-chip. According to the experimental requirements, the designer uses CAD software or other simulation tools to draw the structure and flow path of the chip and then uses micro-nano processing technology to manufacture the chip.
- Cell culture. Add lung cells (such as alveolar epithelial cells, pulmonary vascular endothelial cells, etc.) into the chip and culture them under appropriate culture conditions to make the cells grow and differentiate in the chip.
- Respiratory movement simulation. By controlling the micro air pump, the respiration movement simulation within the chip is realized. The air pump flows gas into the chip, causing volume changes in the alveoli and pulmonary vascular chambers within the chip, thereby simulating the respiratory movement of the human body.
- Oxygen and carbon dioxide exchange. The exchange of oxygen and carbon dioxide within the chip can be achieved by adding an appropriate gas mixture inside the chip. By controlling the gas flow and concentration, the exchange process of oxygen and carbon dioxide in the lungs can be simulated.
- Drug screening and toxicity assessment. Introduce different types of drugs or poisons into the chip, observe the response of cells and the changes of physiological parameters in the chip, so as to evaluate the efficacy and toxicity of drugs.
- Experimental data collection and analysis. The experimental data are collected through the integrated sensors and microscopes on the chip, and the experimental data are processed and analyzed by data analysis tools.
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References
- Francis, I.; et al. Recent advances in lung-on-a-chip models. Drug Discovery Today. 2022 Jun 18.
- Huh, D.; et al. Reconstituting organ-level lung functions on a chip. Science. 2010 Jun 25;328(5986):1662-8.
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