Sorting drops and cells with acoustics: acoustic microfluidic fluorescence-activated cell sorter

Schmid, Lothar; Weitz, David A.; Franke, Thomas

doi:10.1039/c4lc00588k

Cited by 246 publications

(219 citation statements)

References 47 publications

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“…To ensure cells were cut into approximately equal halves we included fluidic shunts immediately downstream of the knife. The shunts helped to equalize the pressure in the two outlets and to avoid disturbance to the cutting process arising from changes in the fluidic resistance at the outlet (22,23). Fig.…”

Section: Resultsmentioning

confidence: 99%

Microfluidic guillotine for single-cell wound repair studies

Blauch

Gai

Khor

et al. 2017

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

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Wound repair is a key feature distinguishing living from nonliving matter. Single cells are increasingly recognized to be capable of healing wounds. The lack of reproducible, high-throughput wounding methods has hindered single-cell wound repair studies. This work describes a microfluidic guillotine for bisecting single Stentor coeruleus cells in a continuous-flow manner. Stentor is used as a model due to its robust repair capacity and the ability to perform gene knockdown in a high-throughput manner. Local cutting dynamics reveals two regimes under which cells are bisected, one at low viscous stress where cells are cut with small membrane ruptures and high viability and one at high viscous stress where cells are cut with extended membrane ruptures and decreased viability. A cutting throughput up to 64 cells per minute-more than 200 times faster than current methods-is achieved. The method allows the generation of more than 100 cells in a synchronized stage of their repair process. This capacity, combined with high-throughput gene knockdown in Stentor, enables time-course mechanistic studies impossible with current wounding methods.

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Section: Resultsmentioning

confidence: 99%

Microfluidic guillotine for single-cell wound repair studies

Blauch

Gai

Khor

et al. 2017

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

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show abstract

“…On the other hand, TSAWs have been used in cross‐type acoustic particle separators to laterally migrate particles and realize separation across the microchannel width or within a sessile droplet, because particles predominantly migrate within the horizontal plane 11, 25, 26, 27. Most SAW‐based acoustofluidic separation techniques utilize forces that act on micro‐objects suspended in a horizontal plane while pushing them laterally inside the microchannel 28, 29, 30, 31, 32. The interaction between TSAWs and the fluid results in leaky acoustic waves that radiate at an angle of ≈22° (in systems comprising water and a lithium niobate (LiNbO 3 ) substrate) inside the microfluidic channel, such that the vertical component ( F v ) of the acoustic radiation force (ARF) acting on the suspended particles is ≈2.5 times greater than the horizontal component of the force ( F h ), i.e., F v ≅ 2.5 F h 33.…”

Section: Introductionmentioning

confidence: 99%

“…(see Figure S1a in the Supporting Information). A multiple‐layered PDMS microchannel with a post beneath the micro‐object manipulation zone was also used in a similar fashion to deflect particles30 and sort cells or droplets 28. IDTs may also be positioned directly beneath a microchannel to induce desired particle migration.…”

Section: Introductionmentioning

confidence: 99%

Vertical Hydrodynamic Focusing and Continuous Acoustofluidic Separation of Particles via Upward Migration

et al. 2017

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A particle suspended in a fluid within a microfluidic channel experiences a direct acoustic radiation force (ARF) when traveling surface acoustic waves (TSAWs) couple with the fluid at the Rayleigh angle, thus producing two components of the ARF. Most SAW‐based microfluidic devices rely on the horizontal component of the ARF to migrate prefocused particles laterally across a microchannel width. Although the magnitude of the vertical component of the ARF is more than twice the magnitude of the horizontal component, it is long ignored due to polydimethylsiloxane (PDMS) microchannel fabrication limitations and difficulties in particle focusing along the vertical direction. In the present work, a single‐layered PDMS microfluidic chip is devised for hydrodynamically focusing particles in the vertical plane while explicitly taking advantage of the horizontal ARF component to slow down the selected particles and the stronger vertical ARF component to push the particles in the upward direction to realize continuous particle separation. The proposed particle separation device offers high‐throughput operation with purity >97% and recovery rate >99%. It is simple in its fabrication and versatile due to the single‐layered microchannel design, combined with vertical hydrodynamic focusing and the use of both the horizontal and vertical components of the ARF.

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“…Examples of such unit operations include encapsulation of single cells inside droplets, injection of reagents into droplets, droplet splitting, and droplet sorting. [6][7][8][9] However, there is still a need for a flexible unit operation to laterally position microparticles or cells in a label-free manner inside droplets. This is useful for the development of droplet washing procedures, or for microparticle enrichment inside droplets, where the final destination of the microparticles after a splitting step must be possible to control.…”

Section: Introductionmentioning

confidence: 99%

Controlled Lateral Positioning of Microparticles Inside Droplets Using Acoustophoresis

et al. 2015

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In this paper, we utilise bulk acoustic waves to control the position of microparticles inside droplets in two-phase microfluidic systems and demonstrate a method to enrich the microparticles. In droplet microfluidics different unit operations are combined and integrated on-chip to miniaturise complex biochemical assays. We present a droplet unit operation capable of controlling the position of microparticles during a trident shaped droplet split. An acoustic standing wave field is generated in the microchannel, and the acoustic forces direct the encapsulated microparticles to the centre of the droplets. The method is generic and requires no labelling of the microparticles, and is operated in a non-contact fashion. It was possible to achieve 2+fold enrichment of polystyrene beads (5 µm in diameter) in the centre daughter droplet with an average recovery of 89% of the beads. Red blood cells were also successfully manipulated inside droplets. These results show the possibility to use acoustophoresis in two-phase systems to enrich microparticles, and opens up for new dropletbased assays that are not possible to perform today.

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Sorting drops and cells with acoustics: acoustic microfluidic fluorescence-activated cell sorter

Cited by 246 publications

References 47 publications

Microfluidic guillotine for single-cell wound repair studies

Microfluidic guillotine for single-cell wound repair studies

Vertical Hydrodynamic Focusing and Continuous Acoustofluidic Separation of Particles via Upward Migration

Controlled Lateral Positioning of Microparticles Inside Droplets Using Acoustophoresis

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