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Sowing the seeds of acoustic trapping : Towards rapid isolation of extracellular vesicles

Havers, Megan LU orcid (2025)
Abstract
Extracellular vesicles (EVs) carry biological information from their parent cell to other cells in the body. To intercept and decipher this information necessitates the isolation of EVs from complex backgrounds such as blood or spinal fluid. Acoustic trapping has been previously demonstrated as a promising technique for EV isolation from cell media, blood plasma and urine. The acoustic fields struggle to directly trap these nanoparticles, however the presence of seed particle clusters can enable sub-micron particles to be trapped. In this work, we combat the limitations of efficiency and throughput in acoustic trapping of nanoparticles by replacing polystyrene seed particles with silica seed particles. The first paper uses model... (More)
Extracellular vesicles (EVs) carry biological information from their parent cell to other cells in the body. To intercept and decipher this information necessitates the isolation of EVs from complex backgrounds such as blood or spinal fluid. Acoustic trapping has been previously demonstrated as a promising technique for EV isolation from cell media, blood plasma and urine. The acoustic fields struggle to directly trap these nanoparticles, however the presence of seed particle clusters can enable sub-micron particles to be trapped. In this work, we combat the limitations of efficiency and throughput in acoustic trapping of nanoparticles by replacing polystyrene seed particles with silica seed particles. The first paper uses model nanoparticles 270 nm polystyrene to visualise the improved trapping efficiency of 40-2000% from suspensions of 1010-1011 particles/ml. Silica-based seed particles experience higher retention forces, allowing faster processing times (less than 10 mins per sample): which is demonstrated for polystyrene nanoparticles (Paper I), plasma EVs (Paper II and IV), and cerebrospinal fluid (Paper III). In the second paper, mass spectrometry based proteomics data demonstrates that acoustically trapping EVs we enrich EV proteins and enable detection of proteins too low in abundance in unprocessed plasma. In the third paper, EVs from cerebrospinal fluid of Alzheimer's patients have been found to contain differing phosphorylated tau proteins (via p-tau 181 and 217 assays) when isolated by acoustic trapping. This requires further investigation to elucidate the relationship between the cargo of brain-derived EVs and pathology. The final paper of this thesis presents a novel technique for co-isolating subpopulations of EVs via antibody-functionalised silica seed particles. Acoustic trapping using silica seed particles shows great promise as a purification step and has already begun to reveal the protein content of extracellular vesicles. Immuno-acoustic trapping opens up the possibilities to also explore the association between the surface proteins that indicate their origin and the internalised cargo of EVs. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof. Oleschuk, Richard, Queen’s University, Canada.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
acoustic trapping, extracellular vesicles, seed particles, microfluidics, acoustofluidics, proteomics
pages
240 pages
publisher
Department of Biomedical Engineering, Lund university
defense location
Lecture Hall Belfragesalen, BMC D13, Sölvegatan 19, Faculty of Engineering LTH, Lund University, Lund.
defense date
2025-05-09 09:00:00
ISBN
978-91-8104-411-9
978-91-8104-410-2
project
Sowing the seeds of acoustic trapping: Towards rapid isolation of extracellular vesicles
language
English
LU publication?
yes
id
0d8dd555-1cfa-4000-bd8f-2f0f494e9022
date added to LUP
2025-04-09 11:23:46
date last changed
2025-05-01 14:49:45
@phdthesis{0d8dd555-1cfa-4000-bd8f-2f0f494e9022,
  abstract     = {{Extracellular vesicles (EVs) carry biological information from their parent cell to other cells in the body. To intercept and decipher this information necessitates the isolation of EVs from complex backgrounds such as blood or spinal fluid. Acoustic trapping has been previously demonstrated as a promising technique for EV isolation from cell media, blood plasma and urine. The acoustic fields struggle to directly trap these nanoparticles, however the presence of seed particle clusters can enable sub-micron particles to be trapped. In this work, we combat the limitations of efficiency and throughput in acoustic trapping of nanoparticles by replacing polystyrene seed particles with silica seed particles. The first paper uses model nanoparticles 270 nm polystyrene to visualise the improved trapping efficiency of 40-2000% from suspensions of 10<sup>10</sup>-10<sup>11</sup> particles/ml. Silica-based seed particles experience higher retention forces, allowing faster processing times (less than 10 mins per sample): which is demonstrated for polystyrene nanoparticles (Paper I), plasma EVs (Paper II and IV), and cerebrospinal fluid (Paper III). In the second paper, mass spectrometry based proteomics data demonstrates that acoustically trapping EVs we enrich EV proteins and enable detection of proteins too low in abundance in unprocessed plasma. In the third paper, EVs from cerebrospinal fluid of Alzheimer's patients have been found to contain differing phosphorylated tau proteins (via p-tau 181 and 217 assays) when isolated by acoustic trapping. This requires further investigation to elucidate the relationship between the cargo of brain-derived EVs and pathology. The final paper of this thesis presents a novel technique for co-isolating subpopulations of EVs via antibody-functionalised silica seed particles. Acoustic trapping using silica seed particles shows great promise as a purification step and has already begun to reveal the protein content of extracellular vesicles. Immuno-acoustic trapping opens up the possibilities to also explore the association between the surface proteins that indicate their origin and the internalised cargo of EVs.}},
  author       = {{Havers, Megan}},
  isbn         = {{978-91-8104-411-9}},
  keywords     = {{acoustic trapping; extracellular vesicles; seed particles; microfluidics; acoustofluidics; proteomics}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Department of Biomedical Engineering, Lund university}},
  school       = {{Lund University}},
  title        = {{Sowing the seeds of acoustic trapping : Towards rapid isolation of extracellular vesicles}},
  url          = {{https://lup.lub.lu.se/search/files/216687133/MeganHaversThesis_Summary.pdf}},
  year         = {{2025}},
}