Simulating drug concentrations in PDMS microfluidic organ chips.

Area of Science:

• Biomedical Engineering
• Pharmacology
• Materials Science

Background:

• Polydimethylsiloxane (PDMS) is widely used for organ-on-a-chip (Organ Chip) devices due to its favorable properties.
• Hydrophobic drug molecules can absorb into PDMS, complicating accurate prediction of drug responses in these models.

Purpose of the Study:

• To develop a combined simulation and experimental approach to predict drug concentration profiles in PDMS Organ Chip devices.
• To enable accurate drug response prediction without prior knowledge of drug partition coefficients (log P).

Main Methods:

• A 3D finite element model was developed to simulate drug absorption, adsorption, convection, and diffusion within the PDMS chip.
• Experimental measurements determined the diffusivity of compounds in PDMS and partition coefficients via mass spectrometry.
• The model was validated using the antimalarial drug amodiaquine in human lung airway chips.

Main Results:

• The study successfully predicted the spatial and temporal drug concentration profiles in PDMS Organ Chip models.
• Experimental derivation of diffusion and partition coefficients allowed for accurate estimation of drug behavior.
• The approach quantitatively estimated amodiaquine concentration profiles in a lung airway-on-a-chip model.

Conclusions:

• This combined simulation and experimental strategy accurately predicts drug concentration gradients in PDMS microfluidic devices.
• The method can be applied to various Organ Chip geometries and surface treatments for enhanced drug testing.
• This approach expands the utility of PDMS Organ Chip devices for preclinical drug evaluation.