The creation of artificial cells, also known as synthetic protocells, is a major challenge in synthetic biology. These systems aim to mimic the compartmentalization and functional organization of living cells, with potential applications in various fields, including drug delivery, biomanufacturing, and understanding the origins of life. A key aspect of creating functional artificial cells is the ability to precisely manipulate and assemble their constituent components. Acoustic manipulation, leveraging the interaction of sound waves with matter, presents a promising tool for this task. Acoustic manipulation techniques offer several advantages for assembling artificial cells, including the ability to manipulate objects in a contactless manner, the lack of need for surface modifications, and the possibility of operating in various environments including air. This research utilizes the TinyLev, a single-axis acoustic levitator, to explore the acoustic manipulation of droplets which could serve as building blocks for artificial cells. The device's ability to controllably position and manipulate multiple droplets in a non-contact manner makes it suitable for complex assembly processes. Understanding the underlying physics of acoustic trapping and the resultant acoustic streaming within the levitated droplets is crucial for designing effective assembly strategies. This study uses computational modeling to investigate the multiphysics processes involved in acoustic trapping and streaming within the TinyLev, providing insights that are valuable for improving the design and operation of acoustic devices used in artificial cell assembly. The focus is on understanding how acoustic forces can be used to precisely position and assemble droplets, paving the way for more complex and functional artificial cell systems.

The paper references several prior studies on artificial cell creation, emphasizing the challenges and existing approaches in assembling complex functional units. There is mention of various techniques used for assembling artificial cells such as microfluidics, self-assembly, and the use of compartmentalized structures like vesicles and coacervates. The literature review highlights the potential of acoustic manipulation as a novel technique for artificial cell assembly. It cites previous works demonstrating acoustic trapping and manipulation of particles, as well as the study of acoustic streaming within confined spaces. The paper specifically mentions relevant research on acoustic levitators and their applications, underscoring the need for detailed multiphysics modeling to better understand and optimize these techniques for artificial cell creation.

The researchers employed computational modeling using COMSOL Multiphysics software (version 5.4) to simulate the acoustic field and particle behavior within the TinyLev acoustic levitator. For the acoustic field simulations, a 3D model of the TinyLev structure was imported into COMSOL. The Pressure Acoustics, Frequency Domain interface was used to solve the Helmholtz equation (∇²p₁ + k²eqp₁ = 0), where p₁ is the total acoustic pressure, k_eq is the wave number, ρ is the density, and c is the speed of sound. No background pressure field was added, simplifying the equation to ∇²p + k²eqp = 0. For modeling the trapping of a 2 mm aqueous droplet in air, the Particle Tracing for Fluid Flow interface was incorporated, enabling the interaction between the acoustic field and the droplet. Acoustic streaming simulations were conducted using a 2D geometry, incorporating models of the artificial cell domain and its sub-compartments. The Thermoviscous Acoustics, Frequency Domain interface was used to solve for the first-order acoustic fields (p₁, u₁, T₁). The Laminar Flow interface was added to solve for the time-averaged net flow, driven by the first-order acoustic fields. Equations (2) and (3) describe these relationships, where subscript 1 refers to the first-order acoustic field and subscript 2 refers to the streaming flow. Stokes drift contributions were included on the boundaries responsible for the streaming effect. Finally, 5 µm diameter particles were released within the model using the Particle Tracing for Fluid Flow interface to study their trajectories under the influence of acoustic streaming. Computational fluid dynamic modeling using a microfluidic module in COMSOL was performed to calculate the tension exerted on the levitated droplet network due to acoustic streaming. This involved integrating the multiplication of fluidic shear rate and fluid viscosity.

The COMSOL simulations successfully modeled the acoustic trapping of droplets within the TinyLev, illustrating the effectiveness of the device for manipulating micro-scale objects. The model accurately represented the complex interplay of acoustic forces and fluid dynamics. The simulations of acoustic streaming provided insights into the flow patterns generated within the levitated droplets. The simulations demonstrated that acoustic streaming exerts significant tension on the droplet network, influencing the stability and arrangement of the droplets. This tension is quantified through computational fluid dynamic modeling. The results reveal the potential of acoustic streaming for actively shaping and manipulating droplet networks for the assembly of artificial cells. The modeling of particle trajectories within the acoustic streaming field highlights the possibilities for precise control over the assembly process. The detailed simulations provide a framework for understanding and optimizing the design parameters of acoustic levitators for applications in artificial cell construction, specifically showing how to leverage acoustic streaming for controlled assembly.

This study provides valuable insights into the multiphysics processes governing acoustic trapping and streaming within a TinyLev acoustic levitator. The ability to accurately model these processes is crucial for designing and optimizing acoustic devices for various applications, particularly in the delicate assembly of artificial cells. The findings demonstrate the potential of acoustic manipulation for creating precise and controlled arrangements of droplets, which could serve as building blocks for more complex artificial cell architectures. The tension generated by acoustic streaming is a critical factor to consider when designing assembly strategies. By understanding this tension, researchers can fine-tune the acoustic parameters to achieve the desired droplet arrangement. The simulations indicate that acoustic streaming may also be useful for mixing components within the droplets or for facilitating reactions within the artificial cell structures. Future work could involve experimental validation of the simulation results, as well as exploring the use of acoustic manipulation in more complex artificial cell assembly processes.

This research successfully employed computational modeling to investigate the multiphysics phenomena involved in acoustic trapping and streaming within a TinyLev levitator. The results demonstrate the potential of acoustic manipulation as a powerful tool for the precise assembly of artificial cells. Future work should focus on experimental validation and the extension of these modeling techniques to more complex artificial cell architectures. Exploring the integration of other manipulation techniques with acoustic levitation could lead to further advancements in artificial cell construction.

The study is primarily based on computational simulations. While the simulations provide valuable insights, experimental validation is needed to confirm the accuracy of the models and their predictions. The simulations make certain assumptions, such as the idealized nature of the droplet and acoustic field, which may not perfectly represent the real-world conditions. Future work should focus on addressing these limitations by validating the simulation results through experimental studies. The 2D simulations of acoustic streaming may not fully capture the complexities of 3D streaming patterns, warranting further investigation using 3D modeling techniques.