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Sample preparation for biomedicine

Manipulation of complex fluids with SAW-based acoustofluidics

Surface acoustic wave (SAW)-based acoustofluidics combines microfluidics with active microacoustic fields. This allows to realize numerous Lab-on-a-Chip operations, reaching from fluid manipulation including mixing, droplet and aerosol generation to the manipulation of cells and (bio-)particles.

SAW-based acoustofluidics & biomedicine

The sorting of specific cells and particles from complex body fluids, i.e. blood, is a critical step in personalized medicine and preparative diagnostics. Current methods reaching from density gradient centrifugation to size-exclusion chromatography are often carried out in a stepwise procedure combining different techniques. Future integrated solutions for handheld or PoC devices, however, require a technology for cell and particle fractionation without the need for sample pre- or posttreatment or cost intensive media, respectively, and with a high cell purity and recovery.

Surface acoustic wave (SAW)-based acoustofluidics is a promising technology to meet this demand, and devices with polydimethylsiloxane (PDMS) microchannels have already demonstrated the ability to manipulate particles and cells. Still, the complexity in fabrication of microchannels on a wafer substrate is a current limit in order to mass produce chips for biomedical purposes.

Innovative acoustofluidic solutions by SAWLab Saxony

At SAWLab Saxony, the Competence and Application Center for Acoustoelectronic Fundamentals, Technologies and Devices, of the Leibniz IFW Dresden (www.SAWLab-Saxony.de) we developed a SAW-based acoustofluidic platform based on lithographically defined, on-chip integrated microfluidic channels to enable precise and reliable large-scale production [1, 2]. To fractionate biomedically relevant cells and particles from complex fluids, a chip layout with two stages with one interdigital transducer (IDT) pair each was designed.

Figure 1a: Acoustofluidic chip with layout for cell and particle sorting

The acoustic field generated by these IDT pairs is driving a pressure gradient in the microchannel fluid by which cells can be influenced based on their intrinsic properties. First, the cells and particles are focused in the first stage and then separated from each other in the second stage due to different in size, density, shape or compressibility. The layout design was verified by measuring the SAW amplitude distribution in the open microchannel. For this purpose, a laser Doppler vibrometer (UHF 120, Polytec GmbH) was used (see Figure 2). 

Figure 1b: On-chip structured microchannel
Figure 2: Measured amplitude distribution inside the microchannel, interdigital transducers (IDTs) of the first stage, f0=13 MHz

Blood cell sorting

Using this chip type, we demonstrated the separation of blood components, i.e. the sorting of erythrocytes and thrombocytes (Figure 1)[3]. A model solution of erythrocytes and thrombocytes in whole blood concentration was supplied through the middle channel inlet. Additionally, a sheath flow was applied. First, all cells were focused in the center of the channel and then the larger erythrocytes were directed to the sides of the microchannel in the acoustic field. The erythrocytes could thus be collected and analyzed at the side outlets, the platelets at the middle one. In total, the platelets could be concentrated by a factor of 7.7 with a purity of 86% and a throughput of 45,000 cells/sec, respectively, making it the currently most advanced two-stage SAW-based thrombocyte sorting technology.

Figure 3: Acoustofluidic setup for the sorting of blood components. Magnified inset of chip shows separation stage: larger erythrocytes are deflected to side outlets and smaller thrombocytes leave through the central outlet

References

1. Winkler, A., et al., Compact SAWaerosol generator. Biomedical Microdevices, 2017. 19(1): p. 10.

2. Winkler, A., et al., SAW-based fluid atomization using mass-producible chip devices. Lab on a Chip, 2015. 15(18): p. 3793-3799.

3.Richard, C., et al., Blood platelet enrichment in mass-producible surface acoustic wave (SAW) driven microfluidic chips. Lab on a Chip, 2019. 19(24): p. 4043-4051.

Images courtnesy: Images courtnesy of the authors unless otherwise specified. Cover image: pinkeyes/shutterstock.com

Our Authors

Melanie Colditz
Leibniz-IFW Dresden, Germany
Romy Kronstein-Wiedemann
TU Dresden / DRK-Blutspendedienst Nord-Ost GmbH, Germany

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