Acoustic Separation of Nanoparticles in Continuous Flow

Wu, Mengxi; Mao, Zhangming; Chen, Kejie; Bachman, Hunter; Chen, Yuchao; Rufo, Joseph; Ren, Liqiang; Li, Peng; Wang, Lin; Huang, Tony Jun

doi:10.1002/adfm.201606039

Cited by 123 publications

(93 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This automated, point-of-care device can further help in advancing exosome-related biomedical research with potential applications in health monitoring, disease diagnostics, and therapeutics. (29)(30)(31)(32)(33)(34). Current acoustic-based separation strategies, however, can only handle biological fluids (such as undiluted blood), which must be preprocessed before exosome separation, and thus require additional equipment and time, and are subject to the risk of sample loss.…”

Section: Significancementioning

confidence: 99%

Isolation of exosomes from whole blood by integrating acoustics and microfluidics

Ouyang

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

751

584

View full text Add to dashboard Cite

Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosomebased biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contactfree manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro-and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contactfree, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine. extracellular vesicles | exosomes | blood-borne vesicles | surface acoustic waves | acoustic tweezers

show abstract

Section: Significancementioning

confidence: 99%

Isolation of exosomes from whole blood by integrating acoustics and microfluidics

Ouyang

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

751

584

View full text Add to dashboard Cite

show abstract

“…So far, the vast majority of successful microscale acoustofluidics applications has been for large (above 2 µm) particles, such as cells, whose dynamics is dom- * jasoba@fysik.dtu.dk † bruus@fysik.dtu.dk inated by the well-characterized, robust acoustic radiation force, which depends on the bulk properties of the acoustic field and material parameters of the particles and the surrounding fluid. However, there is a strong motivation to handle also sub-micrometer particles such as bacteria, exosomes, and viruses, for use in contemporary lab-on-a-chip-based diagnostics and biomedical research [9,[30][31][32]. In contrast to large particles, the dynamics of small (sub-micrometer) particles is dominated by the drag force from the ill-characterized acoustic streaming, and because this streaming is partly driven by the Reynolds stress in the sub-micrometer-thin acoustic boundary layers, it becomes highly sensitive to details of the geometry, motion, and temperature of the confining oscillating walls.…”

Section: Introductionmentioning

confidence: 99%

Theory of pressure acoustics with viscous boundary layers and streaming in curved elastic cavities

Bach

Bruus

2018

The Journal of the Acoustical Society of America

109

View full text Add to dashboard Cite

The acoustic fields and streaming in a confined fluid depend strongly on the viscous boundary layer forming near the wall. The width of this layer is typically much smaller than the bulk length scale set by the geometry or the acoustic wavelength, which makes direct numerical simulations challenging. Based on this separation in length scales, the classical theory of pressure acoustics is extended by deriving a boundary condition for the acoustic pressure that takes viscous boundary-layer effects fully into account. Using the same length-scale separation for the steady second-order streaming, and combining it with time-averaged short-range products of first-order fields, the usual limiting-velocity theory is replaced with an analytical slip-velocity condition on the long-range streaming field at the wall. The derived boundary conditions are valid for oscillating cavities of arbitrary shape and wall motion, as long as both the wall curvature and displacement amplitude are sufficiently small. Finally, the theory is validated by comparison with direct numerical simulation in two examples of two-dimensional water-filled cavities: The well-studied rectangular cavity with prescribed wall actuation, and a more generic elliptical cavity embedded in an externally actuated rectangular elastic glass block.

show abstract

“…For microparticles below a critical size, * weiqiu@fysik.dtu.dk † bruus@fysik.dtu.dk ‡ per.augustsson@bme.lth.se the motion of microparticles is dominated by acoustic streaming, which in many cases hinders the manipulation of sub-micrometer sized particles. Manipulation below the classical limit has previously been demonstrated by flow vortices generated by two-dimensional acoustic fields [29,30], by acoustically active seed particles [24], by a thin reflector design [31], or in systems actuated by surface acoustic waves [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Experimental Characterization of Acoustic Streaming in Gradients of Density and Compressibility

et al. 2019

View full text Add to dashboard Cite

Suppression of boundary-driven Rayleigh streaming has recently been demonstrated for fluids of spatial inhomogeneity in density and compressibility owing to the competition between the boundary-layer-induced streaming stress and the inhomogeneity-induced acoustic body force. Here we characterize acoustic streaming by general defocusing particle tracking inside a half-wavelength acoustic resonator filled with two miscible aqueous solutions of different density and speed of sound controlled by the mass fraction of solute molecules. We follow the temporal evolution of the system as the solute molecules become homogenized by diffusion and advection. Acoustic streaming rolls is suppressed in the bulk of the microchannel for 70-200 seconds dependent on the choice of inhomogeneous solutions. From confocal measurements of the concentration field of fluorescently labelled Ficoll solute molecules, we conclude that the temporal evolution of the acoustic streaming depends on the diffusivity and the initial distribution of these molecules. Suppression and deformation of the streaming rolls are observed for inhomogeneities in the solute mass fraction down to 0.1 %.

show abstract

Acoustic Separation of Nanoparticles in Continuous Flow

Cited by 123 publications

References 72 publications

Isolation of exosomes from whole blood by integrating acoustics and microfluidics

Isolation of exosomes from whole blood by integrating acoustics and microfluidics

Theory of pressure acoustics with viscous boundary layers and streaming in curved elastic cavities

Experimental Characterization of Acoustic Streaming in Gradients of Density and Compressibility

Contact Info

Product

Resources

About