Abstract

Ultrasonic bioreactors have been used for in vitro experimentation to study cellular responses to low-intensity pulsed ultrasound. The presence of an air interface in these bioreactors contributes to variability in the acoustic pressure field, reducing experimental reproducibility. A multiphysics finite element model was developed to simulate the acoustic field in an in-dish ultrasonic bioreactor, where the transducer is immersed in culture medium above the dish surface, and the effects of replacing air below the dish in the bioreactor with a water layer bounded by an acoustic absorbent layer were evaluated. Frequency domain simulations showed that the spatially-averaged pressure at the dish surface alternated between a minimum and maximum level as the distance between the dish and transducer increased. The ratio of the maximum to minimum level was 6.5-fold when the air interface was present, and this ratio dropped to 1.8-fold with replacement of the air interface. However, radial pressure variability was present with or without the air interface in the bioreactor model. Time-dependent simulations showed that the increase in acoustic pressure to a maximum level after US signal activation and the pressure drop after signal cessation were faster when the water-coupled non-reflective layer was used to replace the air layer below the dish, generating a pressure pattern that more closely followed the applied pulsed ultrasound signal due to reduced wave reflection and interference. Overall, this work showed that having water rather than air in contact with the lower dish surface when paired with an acoustic absorbent layer resulted in a less variable pressure field, providing an improved bioreactor design for in vitro experiments.

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