Theranostics 2015; 5(11):1203-1213. doi:10.7150/thno.12295

Research Paper

A Disposable Microfluidic Device for Controlled Drug Release from Thermal-Sensitive Liposomes by High Intensity Focused Ultrasound

Long Meng1 *, Zhiting Deng1 *, Lili Niu1*, Fei Li1, Fei Yan1, Junru Wu2, Feiyan Cai1✉, Hairong Zheng1✉

1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055
2. Department of Physics, University of Vermont, USA
*These authors contributed equally to this work.

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Citation:
Meng L, Deng Z, Niu L, Li F, Yan F, Wu J, Cai F, Zheng H. A Disposable Microfluidic Device for Controlled Drug Release from Thermal-Sensitive Liposomes by High Intensity Focused Ultrasound. Theranostics 2015; 5(11):1203-1213. doi:10.7150/thno.12295. Available from http://www.thno.org/v05p1203.htm

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Abstract

The drug release triggered thermally by high intensity focused ultrasound (HIFU) has been considered a promising drug delivery strategy due to its localized energy and non-invasive characters. However, the mechanism underlying the HIFU-mediated drug delivery remains unclear due to its complexity at the cellular level. In this paper, micro-HIFU (MHIFU) generated by a microfluidic device is introduced which is able to control the drug release from temperature-sensitive liposomes (TSL) and evaluate the thermal and mechanical effects of ultrasound on the cellular drug uptake and apoptosis. By simply adjusting the input electrical signal to the device, the temperature of sample can be maintained at 37 °C, 42 °C and 50 °C with the deviation of ± 0.3 °C as desired. The flow cytometry results show that the drug delivery under MHIFU sonication leads to a significant increase in apoptosis compared to the drug release by incubation alone at elevated temperature of 42 °C. Furthermore, increased squamous and protruding structures on the surface membrane of cells were detected by atomic force microscopy (AFM) after MHIFU irradiation of TSL. We demonstrate that compared to the routine HIFU treatment, MHIFU enables monitoring of in situ interactions between the ultrasound and cell in real time. Furthermore, it can quantitatively analyze and characterize the alterations of the cell membrane as a function of the treatment time.

Keywords: ultrasound-mediated drug delivery, high intensity focused ultrasound, mechanical and thermal effects, microfluidics