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Simulating drug concentrations in PDMS organ chips

2021
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, USA
Microfluidic organ-chip cell cultures are often prepared from polydimethylsiloxane (PDMS) because it is biocompatible, transparent, elastomeric, and permeable to oxygen. However, hydrophobic small molecules can be absorbed on PDMS, which complicates the prediction of drug responses. Here, we describe a combined experimental and computational approach that simulates spatial and temporal drug concentration profiles in 3D under continuous dosing in dual-channel microfluidic organ chips lined with bronchial epithelium and pulmonary microvascular endothelium. This strategy involves the development of a simulation of drug absorption in a PDMS organ chip and experimental quantification of the diffusion and distribution coefficients of the drug. The computational model is then used to estimate the drug concentrations experienced by the cells at each time point in the microfluidic channels of the chip. Applied the method to simulate the concentrations of the antimalarial drug amodiaquine when administered continuously under flow in human lung airway chips. This strategy can estimate the loss of substance due to PDMS absorption in any device composition and should therefore help improve experimental design and analysis of dose-response studies and toxicity studies in PDMS organ chips.
Simulating drug concentrations in PDMS microfluidic organ chips
Donald E. Ingber
#1552
Added on: 09-08-2022
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