Enhanced blood–brain barrier opening induced by focused ultrasound combined with microbubble clusters trapped by an acoustic vortex tweezer

S Shifang Guo (The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,) W Wanlin Jia (The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,) X Xinru Hu (State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical Biology School of Pharmacy East China University of Science and Technology 130 Meilong Road Shanghai 200237 China) Y Yan Li Z Zhen Ya (The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,) C Chaoyu Wang (Department of Chemistry) P Pengfei Xu D Diya Wang (The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,) L Lei Zhang M Mingxi Wan (The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,)

Abstract

Focused ultrasound (FUS) combined with microbubbles (MBs) represents a noninvasive, targeted approach for transiently opening the blood–brain barrier (BBB). While higher MB concentrations can enhance BBB permeability, they also raise the risk of adverse effects such as erythrocyte extravasation. In this study, acoustic vortex (AV) manipulation of MBs was integrated with FUS-mediated BBB opening. The results demonstrated that dispersed MBs could be effectively clustered by an AV tweezer in multi-well plates. Compared with FUS applied to dispersed MBs, the combination of AV, FUS, and MBs required lower acoustic pressure, achieved higher BBB opening efficiency, and elicited significantly stronger stable cavitation. In addition, both pore density and size on cell membranes were greater in the AV + FUS + MB group relative to the FUS + MB group. Importantly, temperature elevation was minimal and cell viability was preserved. These findings suggest that combining FUS with MB clusters trapped by an AV tweezer offers a promising and efficient strategy for BBB opening.

Article Details

Volume / Issue Vol. 138, Issue 16
Published October 28, 2025
ISSN 0021-8979
Publisher American Institute of Physics

Journal Info

Journal of Applied Physics

American Institute of Physics

ISSN: 0021-8979 Physical Sciences

Authors (10)

S

Shifang Guo

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,

W

Wanlin Jia

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,

X

Xinru Hu

State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical Biology School of Pharmacy East China University of Science and Technology 130 Meilong Road Shanghai 200237 China

Y

Yan Li

Z

Zhen Ya

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,

C

Chaoyu Wang

Department of Chemistry

P

Pengfei Xu

D

Diya Wang

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,

L

Lei Zhang

M

Mingxi Wan

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University 1 , Xi'an 710049,