Microfluidic Generation of Monodisperse Nanobubbles by Selective Gas Dissolution

Abstract

and high chemical and bio-activity, [1] NBs find utility in many important fields such as surface physics [2] and chemistry, [3,4] water treatment, [5] surface cleaning, [6] food processing, [7] and nanomedicine. [8] Among these applications, one significant utility of NBs is in clinical diagnostics, [9] where NBs are introduced into blood vessels as ultrasound contrast agents (UCAs), [10] for contrast-enhanced ultrasound (CEUS) imaging. [11] Due to their ability to extravasate out of the bloodstream, NBs may also be well-suited for ultrasound molecular imaging. [12] Specifically, NBs show greater promise than microbubbles (MBs) in molecular imaging of diseases, such as cancer imaging. [13] MBs are intravascular contrast agents because of their larger size, while NB can in principle penetrate through blood vessels to target cells directly, owing to their smaller size and ability to extravasate in tissues due to the enhanced permeability retention (EPR) effect. [14][15][16] The ability to produce monodisperse NBs for drug delivery may achieve significantly improved dose precision. [17] Therapeutic agents can be loaded on, or conjugated to, the surfaces of NBs, and released via ultrasound-induced cavitation. The size

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities

“…Moreover, the shell properties (such as composition, charge) of the microbubbles can be varied by using different lipid mixtures in the continuous phase. Apart from microbubbles, microfluidics can also be used to generate monodisperse nanobubbles, as reported in a recent study [175]. Microfluidics thus provides a promising alternative to conventional agitation/sonication techniques for generating monodisperse bubbles, which could maximize the efficiency of USMB-mediated drug/gene delivery.…”

Biomedical nanobubbles and opportunities for microfluidics

“…20). 149 The nal diameter of the shrunk bubbles can be adjusted by modifying design parameters, including core gas composition and the width of the ow focusing junction. This method offers real-time control over the monodispersity, size, and production rate of the resulting nanobubbles, simply by adjusting the ow conditions, such as gas pressure and liquid ow rate, within the device.…”

“…It is also the rst known method for creating monodisperse nanobubbles, with a favourable polydispersity index of 0.11, at a sufficient throughput for biomedical applications. 149 A drawback of this method is the existence of an upper limit of the bubble concentration, due to the nature of the shrinkage process. To achieve maximum concentration, spherical bubbles must assume a "close-packed" arrangement.…”

“…Our group has recently reported a method for generating monodisperse lipid-shell nanobubbles using a microfluidic device. 149 In this method, monodisperse microbubbles are generated in a microfluidic flow-focusing platform. Shrinkage enables the transformation of microbubbles into nanobubbles.…”

Enhanced tumor accumulation and therapeutic efficacy of liposomal drugs through over-threshold dosing

“…The delivery of as many drugs as possible to solid tumors at the same dose is the key to solving this problem. As delivery vehicles [ 7 ], nanoparticles not only provide a variety of delivery systems for many bioactive insoluble drugs [ 8 , 9 ] but can also protect the active drugs from degradation during blood circulation [ 10 ] to guarantee that more drug molecules are delivered to the targeted site [ 11 – 13 ]. Therefore, nanoparticles for tumor targeting have attracted the attention of many scholars [ 14 – 17 ].…”