Feedback-controlled microbubble generator producing one million monodisperse bubbles per second

TL;DR

This paper introduces a feedback-controlled microbubble generator on a chip that produces up to one million monodisperse bubbles per second with precise size and rate control, advancing ultrasound contrast agent technology.

Contribution

It presents a novel lab-on-a-chip device with real-time optical measurement and feedback control for high-rate, monodisperse microbubble production, enabling better control for medical applications.

Findings

Achieved production rates up to 10^6 bubbles/sec.

Controlled bubble sizes from 2.5 to 20 μm.

Stabilized bubbles at roughly half initial size without losing monodispersity.

Abstract

Monodisperse lipid-coated microbubbles are a promising route to unlock the full potential of ultrasound contrast agents for medical diagnosis and therapy. Here, we present a stand-alone lab-on-a-chip instrument that allows microbubbles to be formed with high monodispersity at high production rates. Key to maintaining a long-term stable, controlled, and safe operation of the microfluidic device with full control over the output size distribution is an optical transmission based measurement technique that provides real-time information on production rate and bubble size. We feed the data into a feedback loop and demonstrate that this system can control the on-chip bubble radius (2.5 to 20 $\mu$m) and the production rate up to $10^6$ bubbles/s. The freshly formed phospholipid-coated bubbles stabilize after their formation to a size approximately two times smaller than their initial on-chip bubble size without loss of monodispersity. The feedback control technique allows for full control over the size distribution of the agent and can aid the development of microfluidic platforms operated by non-specialist end users.