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Acoustic manipulation of cells and microbeads in droplet microfluidics

Fornell, Anna LU (2018)
Abstract
Droplet microfluidics has emerged as a promising platform for miniaturisation of biological assays on-chip. In droplet microfluidics small water droplets (nL-pL) surrounded by an immiscible carrier oil are generated at high throughput. In these droplets particles such as cells or microbeads can be encapsulated, and the idea is that each of these droplets can be used as small reaction chambers for biological analyses. However, one key bottleneck for the full implementation of droplet microfluidics in biology has been the lack of a method to position and enrich particles inside droplets. In this thesis I present for the first time a microfluidic system where cells and microbeads encapsulated inside droplets can be manipulated using acoustic... (More)
Droplet microfluidics has emerged as a promising platform for miniaturisation of biological assays on-chip. In droplet microfluidics small water droplets (nL-pL) surrounded by an immiscible carrier oil are generated at high throughput. In these droplets particles such as cells or microbeads can be encapsulated, and the idea is that each of these droplets can be used as small reaction chambers for biological analyses. However, one key bottleneck for the full implementation of droplet microfluidics in biology has been the lack of a method to position and enrich particles inside droplets. In this thesis I present for the first time a microfluidic system where cells and microbeads encapsulated inside droplets can be manipulated using acoustic standing waves (i.e. acoustophoresis).
The developed microfluidic systems were fabricated in silicon and sealed with glass lids. In the experiments, water droplets containing particles were generated, and an acoustic standing wave-field was created between the channel walls by actuating a piezoelectric transducer attached to the chip. In the first study it was shown that at application of the ultrasound at the first harmonic (1.8 MHz), the encapsulated particles were focused to the centre of the droplets i.e. the pressure node. It was shown that both red blood cells and polystyrene microbeads could be aligned in the centre of the droplets. The usefulness of the technology was proved by combining acoustophoresis with a trident-shaped droplet split to allow for particle enrichment. At application of the ultrasound at the first harmonic close to 90% of the particles were positioned in the centre daughter droplets when approximately 2/3 of the original droplet volume was removed. To better understand the physics of the system, in the second study a theoretical model was developed where the acoustic field inside droplets was investigated. In the third study, switching of encapsulated particles between different microfluidic pathways was shown. At application of the ultrasound at the first harmonic the encapsulated particles were directed into pathway 1 (the centre daughter droplets) while at application of the ultrasound at the second harmonic the encapsulated particles were directed into pathway 2 (the side daughter droplets). In the fourth study, two-dimensional acoustophoresis was used to increase the detectability of particles encapsulated inside droplets by pre-aligning the particles before the droplet generation site. In the fifth and last study, it was demonstrated that acoustophoresis can be used to separate two different particle species originally encapsulated in the same droplet into different daughter droplets based on the acoustic properties of the particles.
This thesis proves that acoustophoresis is a versatile technology that can find various applications in droplet microfluidics. The combination of droplet microfluidics and acoustophoresis opens up for new possibilities for miniaturisation of biological assays on-chip. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Neild, Adrian, Monash University, Australia
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Acoustophoresis, Droplet microfluidics, Enrichment, Lab-on-a-chip, Particle manipulation, Ultrasound
pages
134 pages
publisher
Department of Biomedical Engineering, Lund university
defense location
lecture hall E:1406, building E, Ole Römers väg 3, Lund University, Faculty of Engineering LTH, Lund
defense date
2018-08-24 09:15
ISBN
978-91-7753-727-4
978-91-7753-726-7
language
English
LU publication?
yes
id
b173aa04-f66e-4dc5-9c42-9177f9f6004d
date added to LUP
2018-06-04 10:38:06
date last changed
2018-11-21 21:40:10
@phdthesis{b173aa04-f66e-4dc5-9c42-9177f9f6004d,
  abstract     = {Droplet microfluidics has emerged as a promising platform for miniaturisation of biological assays on-chip. In droplet microfluidics small water droplets (nL-pL) surrounded by an immiscible carrier oil are generated at high throughput. In these droplets particles such as cells or microbeads can be encapsulated, and the idea is that each of these droplets can be used as small reaction chambers for biological analyses. However, one key bottleneck for the full implementation of droplet microfluidics in biology has been the lack of a method to position and enrich particles inside droplets. In this thesis I present for the first time a microfluidic system where cells and microbeads encapsulated inside droplets can be manipulated using acoustic standing waves (i.e. acoustophoresis). <br/>The developed microfluidic systems were fabricated in silicon and sealed with glass lids. In the experiments, water droplets containing particles were generated, and an acoustic standing wave-field was created between the channel walls by actuating a piezoelectric transducer attached to the chip. In the first  study it was shown that at application of the ultrasound at the first harmonic (1.8 MHz), the encapsulated particles were focused to the centre of the droplets i.e. the pressure node. It was shown that both red blood cells and polystyrene microbeads could be aligned in the centre of the droplets. The usefulness of the technology was proved by combining acoustophoresis with a trident-shaped droplet split to allow for particle enrichment. At application of the ultrasound at the first harmonic close to 90% of the particles were positioned in the centre daughter droplets when approximately 2/3 of the original droplet volume was removed. To better understand the physics of the system, in the second study a theoretical model was developed where the acoustic field inside droplets was investigated. In the third study, switching of encapsulated particles between different microfluidic pathways was shown. At application of the ultrasound at the first harmonic the encapsulated particles were directed into pathway 1 (the centre daughter droplets) while at application of the ultrasound at the second harmonic the encapsulated particles were directed into pathway 2 (the side daughter droplets). In the fourth study, two-dimensional acoustophoresis was used to increase the detectability of particles encapsulated inside droplets by pre-aligning the particles before the droplet generation site. In the fifth and last study, it was demonstrated that acoustophoresis can be used to separate two different particle species originally encapsulated in the same droplet into different daughter droplets based on the acoustic properties of the particles.<br/>This thesis proves that acoustophoresis is a versatile technology that can find various applications in droplet microfluidics. The combination of droplet microfluidics and acoustophoresis opens up for new possibilities for miniaturisation of biological assays on-chip.},
  author       = {Fornell, Anna},
  isbn         = {978-91-7753-727-4},
  keyword      = {Acoustophoresis,Droplet microfluidics,Enrichment,Lab-on-a-chip,Particle manipulation,Ultrasound},
  language     = {eng},
  month        = {06},
  pages        = {134},
  publisher    = {Department of Biomedical Engineering, Lund university},
  school       = {Lund University},
  title        = {Acoustic manipulation of cells and microbeads in droplet microfluidics},
  year         = {2018},
}