Recent advances in acoustofluidic separation technology in biology

Abstract

Acoustofluidic separation of cells and particles is an emerging technology that integrates acoustics and microfluidics. In the last decade, this technology has attracted significant attention due to its biocompatible, contactless, and label-free nature. It has been widely validated in the separation of cells and submicron bioparticles and shows great potential in different biological and biomedical applications. This review first introduces the theories and mechanisms of acoustofluidic separation. Then, various applications of this technology in the separation of biological particles such as cells, viruses, biomolecules, and exosomes are summarized. Finally, we discuss the challenges and future prospects of this field.

Keywords: Engineering; Materials science; Nanoscience and technology.

Fig. 1. Different types of acoustic waves.

a Schematic diagram of a surface acoustic wave generator; d represents the width of the finger bar, d’ represents the width between the fingers, M represents the length of the periodic section and W represents the acoustic aperture; b schematic diagram of bulk acoustic waves; c schematic diagram of traveling surface acoustic waves; d schematic diagram of standing surface acoustic waves.

Fig. 2. Schematic diagrams of different types of surface acoustic waves.

a Acoustic streaming effect of traveling surface acoustic waves; b acoustic streaming effect of standing surface acoustic waves; c schematic diagram of the “anechoic corner effect”. The yellow area represents an anechoic domain where the streaming effects and acoustic radiation force are weak, so particles and cells are barely affected.

Fig. 3. Size-based separation using different interdigital transducer designs and positions.

a Focused interdigital transducers were placed beside the microchannel to generate high-energy-density traveling surface acoustic waves for particle separation. Reproduced from ref. with permission from the Royal Society of Chemistry. b A pair of slanted interdigitated transducers placed on the two sides of the microchannel was activated by different frequency signals for particle separation. Reproduced from ref. with permission from the American Chemistry Society. c An interdigital transducer placed under the microchannel was used to separate polystyrene particles of different sizes via vertical migration. Reproduced from ref. with permission from Wiley Online Library. d A pair of tilted-angle interdigital transducers was used to enhance the cell deflection in the microchannel. Reproduced from ref. with permission from the Institute of Electrical and Electronics Engineers.

Fig. 4. Acoustofluidic separation based on nonsize properties.

a Separation of HeLa and MDA-MB-231 cells from peripheral blood mononuclear cells based on the acoustic impedance difference. Reproduced from ref. with permission from the Royal Society of Chemistry. b Separation of polystyrene and polymethyl methacrylate particles with the same diameters based on the differences in particle density and propagation speed of sound using a traveling surface acoustic wave device. Reproduced from ref. with permission from the American Chemistry Society.

Fig. 5. Acoustofluidic separation of cells.

a An acoustic microfluidic trap array to separate cancer cells. Reproduced from ref. with permission from Wiley Online Library. b A microBubble-Activated Acoustic Cell Sorting (BAACS) method to separate HCT 116 colon cancer cells. Reproduced from ref. with permission from SpringerLink. c Bacterial separation from red blood cells based on different acoustophoretic responses using a low-cost plastic bulk acoustic wave-based device. Reproduced from ref. with permission from the Royal Society of Chemistry. d High-throughput separation of red blood cells/white blood cells and platelets from whole blood using a vertical acoustic force. Reproduced from ref. with permission from the Royal Society of Chemistry.

Fig. 6. Acoustofluidic separation of bionanoparticles.

a Separation of Japanese encephalitis virus from complex biological samples. Reproduced from ref. with permission from Elsevier. b Triseparation of proteins from the mixture based on aptamer-coated microparticles and TSAW. Reproduced from ref. with permission from the American Chemistry Society. c Exosome separation from plasma samples using a multistage acoustofluidic device. Reproduced from ref. with permission from Nature.