This review explores the interdisciplinary field of acoustofluidics, which merges acoustics with microfluidics to manipulate fluids and particles at the microscale using sound waves. It examines fundamental concepts, including acoustic wave types such as Surface Acoustic Waves (SAW) and Bulk Acoustic Waves (BAW). Applications in microfluidic devices like particle sorting, mixing, and medium switching are emphasized. Additionally, the review addresses the advantages, challenges, and future directions of these technologies, emphasizing their role in advancing lab-on-a-chip innovations and enhancing microfluidic device capabilities. Notable recent advances include single-cell analysis, point-of-care diagnostics, and tissue engineering applications.
Acoustofluidics is an interdisciplinary field that combines acoustics and microfluidics to manipulate fluids and particles at the microscale using sound waves. Emerging from advancements in microfabrication, it allows for precise, contactless control over processes such as particle sorting and separation based on properties like shape, flexibility, and activity. This makes it invaluable in medical, biological, and chemical analyses. Acoustic waves, owing to their efficiency and biocompatibility, are particularly effective for sorting particles of all sizes. Recent advancements have also integrated dynamic field manipulation and multi-resonator designs to expand its capabilities.
Acoustofluidics involves the manipulation of particles and fluids using acoustic waves, which are mechanical vibrations traveling through air, liquid, or solid media. These waves generate forces that control particle movement, separation, and concentration at the microscale. The tunability and non-invasive nature of these forces make acoustofluidics particularly useful in biological and chemical applications. Key factors influencing these interactions include wave frequency, amplitude, particle properties (size, density, compressibility), and the propagation medium. Understanding these principles is crucial for optimizing device performance in complex systems. Acoustic forces include:
Recent computational approaches, such as finite element methods (e.g., COMSOL), have improved the modelling and understanding of these forces, aiding in device optimization.
Acoustofluidics employs two primary wave types:
Acoustofluidic systems are highly specialized assemblies that integrate cutting-edge components to precisely manipulate fluids and particles at the microscale. These systems combine mechanical precision with optical monitoring, making them versatile tools for research and industrial applications ranging from biological analysis to chemical processing.
Modern setups integrate laser Doppler vibrometers and hydrophones for precise field measurements. Additionally, metasurfaces and holographic elements enable tailored acoustic field patterns for complex applications.
Despite their advantages, organoids face several limitations:
Cell sorting using acoustofluidics provides a contact-free and biocompatible method for separating cells based on their size, density, and mechanical properties. This approach is particularly valuable for applications where maintaining cell viability and function is critical, such as isolating rare cell populations (e.g., circulating tumor cells or stem cells) for diagnostic and therapeutic purposes. The ability to sort cells efficiently and gently without the use of harsh chemicals or mechanical stress ensures that the sorted cells retain their natural characteristics, making them suitable for downstream applications in research, medicine, and biotechnology. There are several ways for cell sorting using acoustofluidics:
Particles move to pressure nodes based on size, with larger particles experiencing stronger acoustic radiation forces. Tilted-angle standing SAWs improve sorting efficiency, and advanced designs now handle highly concentrated solutions effectively.
Preloaded micron-sized particles trap targets via secondary radiation forces, allowing separation based on density and compressibility. Acoustic contrast factor-based binary separations are widely applied in medical diagnostics and lipid emboli removal.
By tuning wave frequencies, particles align at specific pressure nodes. Multi-resonator designs allow simultaneous sorting of multiple populations, improving throughput for complex biological samples.
Acoustic tweezers are advanced tools that use highly focused acoustic waves to manipulate individual particles or cells with precision. By generating localized acoustic radiation forces, these tweezers can trap and move cells without direct contact, ensuring minimal physical or chemical interference. Acoustic tweezers provide a powerful tool for the precise manipulation of individual cells, enabling detailed studies of cell-cell interactions and signaling. Recent advancements, such as acoustical vortex tweezers, offer enhanced selectivity and minimal biological impact, preserving cell viability during manipulation. Additionally, acoustic force spectroscopy has emerged as a valuable technique for probing the mechanical properties of cells, including measurements of T-cell adhesion strength and red blood cell deformability, providing insights into cellular biomechanics and pathophysiology.
Acoustic waves play a critical role in advancing 3D cell culture techniques, particularly for tissue engineering and organoid assembly. By leveraging acoustic forces, researchers can aggregate and pattern cells with precision, facilitating the creation of complex tissue structures. Acoustic streaming further enhances these processes by enabling efficient scaffold patterning and the manipulation of organoids in a contact-free manner. This approach ensures minimal disruption to cell integrity while promoting the assembly of functional biological tissues for research and therapeutic applications.
Acoustofluidics enhances liquid handling for applications like point-of-care diagnostics, reducing contamination risks and improving workflow efficiency. An example is liquid biopsy, where recent methods differentiate nanometer- to micrometer-sized particles, such as liposomes, exosomes, and circulating tumor cells (CTC).
Fluid mixing is a critical process in microfluidic systems, and acoustofluidics provides an innovative approach to enhance mixing efficiency. Acoustic waves, when applied to a fluid, generate acoustic streaming patterns that create localized vortices and enhance fluid movement. These streaming patterns overcome the challenges of laminar flow typically observed in microfluidic channels, where mixing is limited by diffusion. By employing sharp-edged structures or asymmetric geometries in the microchannel design, the acoustic streaming effect is amplified, leading to more efficient and rapid mixing of reactants. This capability is particularly valuable in chemical reactions, biochemical assays, and sample preparation, where uniform mixing is essential for accuracy and reproducibility. Additionally, acoustofluidic mixing methods are contact-free and do not require mechanical agitation, preserving the integrity of sensitive biological samples or delicate chemical reactions. The ability to precisely control mixing parameters by adjusting wave frequency and amplitude further enhances the versatility of this technique, making it indispensable for applications in diagnostics, drug delivery, and chemical synthesis.
Using acoustic waves is also a good way to change particles from a solution to another. The flows in microfluidic channels are laminar. It is then possible to have two laminar streams flowing parallel to each other in a microfluidic channel. By applying an acoustic wave, it is possible to move particles from one stream to the other. The buffer switch is equivalent to a centrifugal wash. Different designs to complete the buffer switch have been reported: a layered resonator (Hawkes et al, 2004), a microfluidic channel with two inlets and two outlets (Liu et al, 2012), a transversal resonator (Petersson et al, 2005) and a device with several inlets and outlets located on the side of the channel (Augustsson et al, 2009).
The use of acoustophoresis reduces the analysis time and the risk of errors as several centrifugation steps are not needed any more. This technique is also of great interest in order to pull out rare species present in complex solutions.
Acoustofluidics offers transformative benefits that make it an essential technology in modern microfluidics, enabling precise and efficient manipulation of fluids and particles across various scientific and industrial domains:
Acoustofluidics faces several challenges that require attention for widespread adoption and optimization:
Acoustofluidics stands at the intersection of acoustics and microfluidics, offering revolutionary methods for microscale particle and fluid manipulation. Applications like particle sorting, and fluid mixing highlight its importance in scientific research. Addressing challenges such as energy efficiency and standardization will drive further innovation, unlocking new capabilities for microfluidic devices. The integration of advanced tools, such as dynamic field manipulation and metasurfaces, is paving the way for transformative progress in biomedical diagnostics and tissue engineering.
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