Horizon: Microfluidic platform for the production of therapeutic microbubbles and nanobubbles

Microbubbles (MBs) have a multitude of applications including as contrast agents in ultrasound imaging and as therapeutic drug delivery vehicles, with further scope for combining their diagnostic and therapeutic properties (known as theranostics). MBs used clinically are commonly made by mechanical agitation or sonication methods, which offer little control over population size and dispersity. Furthermore, clinically used MBs are yet to be used therapeutically and further research is needed to develop these theranostic agents. In this paper, we present our MB production instrument Horizon, which is a robust, portable, and user-friendly instrument, integrating the key components for producing MBs using microfluidic flow-focusing devices. In addition, we present the system design and specifications of Horizon and the optimized protocols that have so far been used to produce MBs with specific properties. These include MBs with tailored size and low dispersity (monodisperse); MBs with a diameter of similar to 2 mu m, which are more disperse but also produced in higher concentration; nanobubbles with diameters of 100-600 nm; and therapeutic MBs with drug payloads for targeted delivery. Multiplexed chips were able to improve production rates up to 16-fold while maintaining production stability. This work shows that Horizon is a versatile instrument with potential for mass production and use across many research facilities, which could begin to bridge the gap between therapeutic MB research and clinical use. (c) 2021 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This paper presents a new instrument called Horizon for producing microbubbles, which is robust, portable, and user-friendly, capable of producing microbubbles with specific properties including monodisperse microbubbles, more disperse but higher yield microbubbles, nanobubbles, and therapeutic microbubbles with drug payloads. Multiplexed chips can improve production rates up to 16-fold while maintaining production stability. This work suggests that Horizon is a versatile instrument with potential for mass production and widespread use in research facilities to bridge the gap between therapeutic microbubble research and clinical applications.