Microfluidic separation technology has garnered significant attention over the past decade where particles are being separated at a micro/nanoscale in a rapid, low-cost, and simple manner. Amongst a myriad of separation technologies that have emerged thus far, acoustic microfluidic separation techniques are extremely apt to applications involving biological samples attributed to various advantages, including high controllability, biocompatibility, and non-invasive, label-free features. With that being said, downsides such as low throughput and dependence on external equipment still impede successful commercialization from laboratory-based prototypes. Here, we present a comprehensive review of recent advances in acoustic microfluidic separation techniques, along with exemplary applications. Specifically, an inclusive overview of fundamental theory and background is presented, then two sets of mechanisms underlying acoustic separation, bulk acoustic wave and surface acoustic wave, are introduced and discussed. Upon these summaries, we present a variety of applications based on acoustic separation. The primary focus is given to those associated with biological samples such as blood cells, cancer cells, proteins, bacteria, viruses, and DNA/RNA. Finally, we highlight the benefits and challenges behind burgeoning developments in the field and discuss the future perspectives and an outlook towards robust, integrated, and commercialized devices based on acoustic microfluidic separation.

Active and passive techniques for bubble trapping and control in various microfluidic applications.

The majority of microfluidic devices nowadays are built on rigid or bulky substrates such as glass slides and polydimethylsiloxane (PDMS) slabs, and heavily rely on external equipment such as syringe pumps. Although a variety of micropumps have been developed in the past, few of them are suitable for flexible microfluidics or lab-on-a-foil systems. In this paper, stick-and-play acoustic micropump is built on thin and flexible plastic film by printing microstructures termed defended oscillating membrane equipped structures (DOMES) using two-photon polymerization. Specifically, this new micropump induces rectified flow upon the actuation of acoustic waves, and the flow patterns agree with simulation results very well. More importantly, the developed micropump has the capabilities to generate adjustable flow rates as high as 420 nL min⁻¹, and does not suffer from problems such as bubble instability, gas dissolution, and undesired bubble-trapping that commonly occur in other forms of acoustic micropumps. Since the micropump works in stick-and-play mode, it is reusable after cleaning thanks to the easy separation of covers and substrates. Lastly, the developed micropump is applied for creating a self-pumped single-cell trapping device. The excellent trapping capability of the integrated device proves its potential for long-term studies of biological behaviors of individual cells for biomedical applications.