Acoustofluidic rare cell sample preparation
Author
Summary, in English
Acoustofluidics utilizes a combination of acoustics, in the form of ultrasound, and microfluidics to manipulate cells
and particles. This has proven to be a versatile method that is gentle to the cells. In this thesis acoustofluidics has been used for
processing rare cells in continuous flow. Rare cells are within this thesis defined as cells that are present in numbers of 1-1000
per mL in a much larger population of background cells. Rare cells present in blood have been of particular interest, and cancer
cells and bacteria have been used as model cells. In this thesis acoustofluidics has first been used to concentrate cells. This was
done by using two-dimensional focusing and a multistage acoustofluidic device where sequential concentration steps,
generating moderate concentration factors, could be multiplied into large concentration factors. The usefulness of the method
was then extended as the critical particle focusing size was lowered to also allow focusing of bacteria. This was done through
using two-dimensional focusing, which was shown to change the acoustic streaming pattern to no longer counteract the primary
acoustic radiation force. The new critical particle focusing size was determined to be between 0.5 μm and 0.24 μm in particle
diameter for polystyrene-like particles. In the third paper a simplyfied acoustofluidic device, that does not rely on a clean fluid
sheath flow to prealign the cells or particles before the separation, was presented. To be able to do this the device used only
two-dimensional focusing to prealign the cells. The usefulness of the device was in turn demonstrated with the separation of
cancer cells from white blood cells where it was shown to perform comparably to previously presented devices. In the fourth
paper a separation method was combined with the concentration method presented in the first paper on an integrated device.
The device was shown to be able to simultaneously separate and concentrate cancer cells from white blood cells. Finally, the
previously proposed concentration device was integrated with a DEP single cell trapping device further showing the usefulness
of the acoustofluidic method. Standing alone, the DEP trapping device could only process sample at a flow rate of 4 μL/min
while still maintaining a high trapping efficiency.By integrating the DEP trapping device with the acoustofluidic concentrator
device a higher sample inflow rate could be used as the acoustofluidic device could gear down the flow rate before the sample
entered the DEP trapping device. Together samples could be processed ~10 times faster than using the DEP trapping device
alone, while still recovering over 90% of the cells.
and particles. This has proven to be a versatile method that is gentle to the cells. In this thesis acoustofluidics has been used for
processing rare cells in continuous flow. Rare cells are within this thesis defined as cells that are present in numbers of 1-1000
per mL in a much larger population of background cells. Rare cells present in blood have been of particular interest, and cancer
cells and bacteria have been used as model cells. In this thesis acoustofluidics has first been used to concentrate cells. This was
done by using two-dimensional focusing and a multistage acoustofluidic device where sequential concentration steps,
generating moderate concentration factors, could be multiplied into large concentration factors. The usefulness of the method
was then extended as the critical particle focusing size was lowered to also allow focusing of bacteria. This was done through
using two-dimensional focusing, which was shown to change the acoustic streaming pattern to no longer counteract the primary
acoustic radiation force. The new critical particle focusing size was determined to be between 0.5 μm and 0.24 μm in particle
diameter for polystyrene-like particles. In the third paper a simplyfied acoustofluidic device, that does not rely on a clean fluid
sheath flow to prealign the cells or particles before the separation, was presented. To be able to do this the device used only
two-dimensional focusing to prealign the cells. The usefulness of the device was in turn demonstrated with the separation of
cancer cells from white blood cells where it was shown to perform comparably to previously presented devices. In the fourth
paper a separation method was combined with the concentration method presented in the first paper on an integrated device.
The device was shown to be able to simultaneously separate and concentrate cancer cells from white blood cells. Finally, the
previously proposed concentration device was integrated with a DEP single cell trapping device further showing the usefulness
of the acoustofluidic method. Standing alone, the DEP trapping device could only process sample at a flow rate of 4 μL/min
while still maintaining a high trapping efficiency.By integrating the DEP trapping device with the acoustofluidic concentrator
device a higher sample inflow rate could be used as the acoustofluidic device could gear down the flow rate before the sample
entered the DEP trapping device. Together samples could be processed ~10 times faster than using the DEP trapping device
alone, while still recovering over 90% of the cells.
Department/s
- Department of Biomedical Engineering
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2015
Language
English
Full text
- Available as PDF - 28 MB
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Document type
Dissertation
Topic
- Other Medical Engineering
Status
Published
Supervisor
ISBN/ISSN/Other
- ISBN: 978-91-7623-527-0
Defence date
11 December 2015
Defence time
09:15
Defence place
Lecture hall 1406, building E, Ole Römers väg 3, Lund University, Faculty of Engineering LTH, Lund
Opponent
- Abraham Lee