技術論文とプレゼンテーション

Acoustic manipulation of cells offers a label-free, contactless method for a microfluidic platform for precise cell handling, cell analysis, investigation of cell–cell interactions, and 3D cell culture applications. With few exceptions, existing acoustic manipulation chips typically use single-cavity systems, limiting their capability for parallel 3D cell/spheroid analysis required for life science studies. This study presents a numerical analysis of the CellLEGO acoustofluidic platform, a 3D cell analysis tool featuring an array of 100 spherical cavities that mimic a standardized 96-well plate for microscopy analysis. The objective of this work is to conduct a comprehensive simulation study to generate stable trapping regions in a multi-cavity chip using bulk acoustic waves. This was achieved by analyzing Eigenmodes, frequency response, acoustic pressure distributions, temperature rise, shear rates, and particle trajectories in COMSOL Multiphysics. The model primarily consists of fluid-filled cavities interconnected by micron-sized channels, which allow continuous flow while keeping cells drift-free within the microscope's depth-of-field. For the simulation, the pressure acoustics, frequency domain interface was used for frequency-domain analysis. The thermoviscous boundary layer condition was imposed at the fluid boundaries to simulate thermal and viscous loss at microscale interfaces. An Eigenfrequency study was conducted to determine the Eigenfrequencies of the multi-cavity system and identify the dominant acoustic modes near the target driving frequency. Then, a frequency-domain study was conducted over the target frequency range to compare pressure amplitudes, node positions, and the consistency of the pressure fields across different cavities. In the perfused environment, the laminar flow interface was coupled to estimate the velocity, fluid pressure, and shear rate distributions in the channels. To assess the thermal load of the glass chip, the heat transfer interface was used to estimate the temperature increase inside the chip under acoustic excitation and room temperature conditions. The Eigenfrequency study showed that near 2 MHz, the cavities generated pressure fields similar to those produced by low-order spherical acoustic modes with a Bessel-like Eigenmode distribution. Such mode generation leads to the formation of stable trapping regions near the center of the trap cavity. Hence, subsequent frequency-domain simulations were performed near 2 MHz with the highest trapping force. Using a single piezo transducer, multiple stable acoustic fields can be generated in the cavities, with pressure nodes (regions of minimum potential energy) generally located at the center of each cavity, thus creating reliable trapping sites for cells/microparticles. The flow simulations showed that the shear rate at the trapping region in the proposed chip geometry and perfusion rate was relatively low, minimizing fluid shear impact on the cells. The thermal simulations estimated a temperature increase of only 0.06 °C under operating conditions, demonstrating good thermal stability. Finally, the particle trajectory analysis showed that particles in a realistic flow and acoustic field converge to the cavity center and get trapped. This numerical simulation work aims to provide a theoretical basis for the development of multi-cavity acoustofluidic chips, including optimal selection of driving frequency and parallelized cell experiments.