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An acoustic device for ultra high-speed quantification of cell strain during cell-microbubble interaction

An acoustic device for ultra high-speed quantification of cell strain during cell-microbubble interaction
An acoustic device for ultra high-speed quantification of cell strain during cell-microbubble interaction

Microbubbles utilize high-frequency oscillations under ultrasound stimulation to induce a range of therapeutic effects in cells, often through mechanical stimulation and permeabilization of cells. One of the largest challenges remaining in the field is the characterization of interactions between cells and microbubbles at therapeutically relevant frequencies. Technical limitations, such as employing sufficient frame rates and obtaining sufficient image resolution, restrict the quantification of the cell's mechanical response to oscillating microbubbles. Here, a novel methodology was developed to address many of these limitations and improve the image resolution of cell-microbubble interactions at high frame rates. A compact acoustic device was designed to house cells and microbubbles as well as a therapeutically relevant acoustic field while being compatible with a Shimadzu HPV-X camera. Cell viability tests confirmed the successful culture and proliferation of cells, and the attachment of DSPC- and cationic DSEPC-microbubbles to osteosarcoma cells was quantified. Microbubble oscillation was observed within the device at a frame rate of 5 million FPS, confirming suitable acoustic field generation and ultra high-speed image capture. High spatial resolution in these images revealed observable deformation in cells following microbubble oscillation and supported the first use of digital image correlation for strain quantification in a single cell. The novel acoustic device provided a simple, effective method for improving the spatial resolution of cell-microbubble interaction images, presenting the opportunity to develop an understanding of the mechanisms driving the therapeutic effects of oscillating microbubbles upon ultrasound exposure.

acoustic device, cell strain, digital image correlation, microbubbles, ultra high-speed imaging, ultrasound
2373-9878
5912–5923
Pattinson, Oliver
7325d377-815d-4f54-a67e-597244c7f77b
Keller, Sara B.
3c7d3473-ed72-4260-9692-99bafb774aa3
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Pierron, Fabrice
a1fb4a70-6f34-4625-bc23-fcb6996b79b4
Carugo, Dario
cf740d40-75f2-4073-9c6e-6fcf649512ca
Pattinson, Oliver
7325d377-815d-4f54-a67e-597244c7f77b
Keller, Sara B.
3c7d3473-ed72-4260-9692-99bafb774aa3
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Pierron, Fabrice
a1fb4a70-6f34-4625-bc23-fcb6996b79b4
Carugo, Dario
cf740d40-75f2-4073-9c6e-6fcf649512ca

Pattinson, Oliver, Keller, Sara B., Evans, Nicholas D., Pierron, Fabrice and Carugo, Dario (2023) An acoustic device for ultra high-speed quantification of cell strain during cell-microbubble interaction. ACS Biomaterials Science & Engineering, 9 (10), 5912–5923. (doi:10.1021/acsbiomaterials.3c00757).

Record type: Article

Abstract

Microbubbles utilize high-frequency oscillations under ultrasound stimulation to induce a range of therapeutic effects in cells, often through mechanical stimulation and permeabilization of cells. One of the largest challenges remaining in the field is the characterization of interactions between cells and microbubbles at therapeutically relevant frequencies. Technical limitations, such as employing sufficient frame rates and obtaining sufficient image resolution, restrict the quantification of the cell's mechanical response to oscillating microbubbles. Here, a novel methodology was developed to address many of these limitations and improve the image resolution of cell-microbubble interactions at high frame rates. A compact acoustic device was designed to house cells and microbubbles as well as a therapeutically relevant acoustic field while being compatible with a Shimadzu HPV-X camera. Cell viability tests confirmed the successful culture and proliferation of cells, and the attachment of DSPC- and cationic DSEPC-microbubbles to osteosarcoma cells was quantified. Microbubble oscillation was observed within the device at a frame rate of 5 million FPS, confirming suitable acoustic field generation and ultra high-speed image capture. High spatial resolution in these images revealed observable deformation in cells following microbubble oscillation and supported the first use of digital image correlation for strain quantification in a single cell. The novel acoustic device provided a simple, effective method for improving the spatial resolution of cell-microbubble interaction images, presenting the opportunity to develop an understanding of the mechanisms driving the therapeutic effects of oscillating microbubbles upon ultrasound exposure.

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Accepted/In Press date: 11 September 2023
e-pub ahead of print date: 25 September 2023
Published date: 25 September 2023
Additional Information: Funding Information: This work is funded by the ESPRC in a studentship for the PhD of Oliver Pattinson. The authors would like to thank Dr. Alex Marek for assistance in the use of the Shimadzu camera and 3D printing molds for the device. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.
Keywords: acoustic device, cell strain, digital image correlation, microbubbles, ultra high-speed imaging, ultrasound

Identifiers

Local EPrints ID: 482475
URI: http://eprints.soton.ac.uk/id/eprint/482475
ISSN: 2373-9878
PURE UUID: 4b4de8f4-1f14-4193-a7a9-1cdafc5879f5
ORCID for Nicholas D. Evans: ORCID iD orcid.org/0000-0002-3255-4388
ORCID for Fabrice Pierron: ORCID iD orcid.org/0000-0003-2813-4994

Catalogue record

Date deposited: 09 Oct 2023 16:38
Last modified: 18 Mar 2024 03:16

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Contributors

Author: Sara B. Keller
Author: Fabrice Pierron ORCID iD
Author: Dario Carugo

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