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Investigation of Polymer-Shelled Microbubble Motions in Acoustophoresis
KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. (Contrast enhanced ultrasound imaging)ORCID iD: 0000-0003-0129-3442
KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden .ORCID iD: 0000-0003-1264-1254
Diapartimento di Chimica, Università di Roma Tor Vergata.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The objective of this paper is to explore the trajectory motion of microsize (typically smaller than a redblood cell) encapsulated polymer-shelled gas bubbles propelled by radiation force in an acousticstanding-wave field and to compare the corresponding movements of solid polymer microbeads. Theexperimental setup consists of a microfluidic chip coupled to a piezoelectric crystal (PZT) with aresonance frequency of about 2.8 MHz. The microfluidic channel consists of a rectangular chamberwith a width, w, corresponding to one wavelength of the ultrasound standing wave. It creates one fullwave ultrasound of a standing-wave pattern with two pressure nodes at4w and43w and threeantinodes at 0,2w , and w. The peak-to-peak amplitude of the electrical potential over the PZT wasvaried between 1 and 10 volts. From Gor’kov’s potential equation, the acoustic contrast factor, Φ, forthe polymer-shelled microbubbles was calculated to about -60.7. Experimental results demonstratethat the polymer-shelled microbubbles are translated and accumulated at the pressure antinode planes.This trajectory motion of polymer-shelled microbubbles toward the pressure antinode plane is similarto what has been described for other acoustic contrast particles with a negative Φ. First, primaryradiation forces dragged the polymer-shelled microbubbles into proximity with each other at thepressure antinode planes. Then, secondary radiation forces caused them to aggregate at different spotsalong the channel. The relocation time for polymer-shelled microbubbles was 40 times shorter thanthat for polymer microbeads, and in contrast to polymer microbeads, the polymer-shelledmicrobubbles were actuated even at driving voltages (proportional to radiation forces) as low as 1 volt.In short, the polymer-shelled microbubbles demonstrate the behavior attributed to the negativeacoustic contrast factor particles and thus can be trapped at the antinode plane and thereby seperatedfrom solid particles, such as cells. This phenomenon could be utilized in exploring future applications,such as bioassay, bioaffinity, and cell interaction studies in vitro in a well-controlled environment.

Keyword [en]
Acoustophoresis, Ultrasound contrast agent, Radiation force, Ultrasound standing wave, Acoustic contrast factor
National Category
Biomedical Laboratory Science/Technology
Research subject
Physics; Fibre and Polymer Science; Medical Technology
Identifiers
URN: urn:nbn:se:kth:diva-172391OAI: oai:DiVA.org:kth-172391DiVA: diva2:847579
Projects
3MiCRON
Funder
EU, FP7, Seventh Framework Programme, 245572
Note

QS 2015. This manuscript is review process.

Available from: 2015-08-20 Created: 2015-08-20 Last updated: 2015-08-26Bibliographically approved
In thesis
1. Nano-Engineered Contrast Agents: Toward Multimodal Imaging and Acoustophoresis
Open this publication in new window or tab >>Nano-Engineered Contrast Agents: Toward Multimodal Imaging and Acoustophoresis
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diagnostic ultrasound (US) is safer, quicker and cheaper than other diagnostic imaging modalities. Over the past two decades, the applications of US imaging has been widened due to the development of injectable, compressible and encapsulated microbubbles (MBs) that provide an opportunity to improve conventional echocardiographic imaging, blood flow assessment and molecular imaging. The encapsulating material is manufactured by different biocompatible materials such as proteins, lipids or polymers. In current research, researchers modify the encapsulated shell with the help of advanced molecular chemistry techniques to load them with dyes (for fluorescent imaging), nanoparticles and radioisotopes (for multimodal imaging) or functional ligands or therapeutic gases (for local drug delivery). The echogenicity and the radial oscillation of MBs is the result of their compressibility, which undoubtedly varies with the encapsulated shell characteristics such as rigidity or elasticity.

In this thesis, we present acoustic properties of novel type of polyvinyl alcohol (PVA)-shelled microbubble (PVA-MB) that was further modified with superparamagnetic iron oxide nanoparticles (SPIONs) to work as a dual-modal contrast agent for magnetic resonance (MR) imaging along with US imaging. Apparently, the shell modification changes their mechanical characteristics, which affects their acoustic properties. The overall objective of the thesis is to investigate the acoustic properties of modified and unmodified PVA-MBs at different ultrasound parameters.

The acoustic and mechanical characterization of SPIONs modified PVA-MBs revealed that the acoustical response depends on the SPION inclusion strategy. However they retain the same structural characteristics after the modification. The modified MBs with SPIONs included on the surface of the PVA shell exhibit a soft-shelled behavior and produce a higher echogenicity than the MBs with the SPIONs inside the PVA shell. The fracturing mechanism of the unmodified PVA-MBs was identified to be different from the other fracturing mechanisms of conventional MBs. With the interaction of high-pressure bursts, the air gas core is squeezed out through small punctures in the PVA shell. During the fracturing, the PVA-MBs exhibit asymmetric (other modes) oscillations, resulting in sub- and ultra-harmonic generation. Exploiting the US imaging at the other modes of the oscillation of the PVA-MBs would provide an opportunity to visualize very low concentrations of (down to single) PVA-MBs. We further introduced the PVA-MBs along with particles mimicking red blood cells in an acoustic standing-wave field to observe the acoustic radiation force effect. We observed that the compressible PVA-MBs drawn toward pressure antinode while the solid blood phantoms moved toward the pressure node. This acoustic separation method (acoustophoresis) could be an efficient tool for studying the bioclearance of the PVA-MBs in the body, either by collecting blood samples (in-vitro) or by using the extracorporeal medical procedure (ex-vivo) at different organs.

Overall, this work contributes significant feedback for chemists (to optimize the nanoparticle inclusion) and imaging groups (to develop new imaging sequences), and the positive findings pave new paths and provide triggers to engage in further research. 

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. x, 53 p.
Series
TRITA-STH : report, ISSN 1653-3836 ; 2015:5
Keyword
Nano-engineered microbubbles, SPION nanoparticles, Acoustic characterization of MBs, Fracturing mechanism of MBs, Opto-acoustics, Acoustophoresis
National Category
Medical Laboratory and Measurements Technologies Medical Image Processing Nano Technology Signal Processing Polymer Technologies
Research subject
Physics; Järnvägsgruppen - Ljud och vibrationer; Technology and Health
Identifiers
urn:nbn:se:kth:diva-172397 (URN)978-91-7595-648-0 (ISBN)
Public defence
2015-09-22, 3221, Alfred Nobels Álle 8, Hudding, 09:00 (English)
Opponent
Supervisors
Projects
3MiCRON
Funder
EU, FP7, Seventh Framework Programme, 245572
Note

QC 20150827

Available from: 2015-08-26 Created: 2015-08-20 Last updated: 2015-08-27Bibliographically approved

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Kothapalli, Satya V.V.N.Janerot Sjöberg, BirgittaGrishenkov, Dmitry

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