Droplet microfluidics to prepare magnetic polymer vesicles and to confine the heat in magnetic hyperthermia

TL;DR

This paper introduces microfluidic techniques to produce magnetic polymer vesicles and magnetic droplets, enabling efficient hyperthermia heating at small scales for potential cancer therapy applications.

Contribution

It presents novel microfluidic methods for creating magnetic vesicles and droplets, improving process speed and control for hyperthermia applications.

Findings

Magnetic vesicles can be produced rapidly using a double-emulsion process.

Magnetic droplets generate measurable heat under RF magnetic fields at nanoliter scale.

Heat transfer models help understand minimum tumor size for hyperthermia treatment.

Abstract

In this work, we present two types of microfluidic chips involving magnetic nanoparticles dispersed in cyclohexane with oleic acid. In the first case, the hydrophobically coated nanoparticles are self-assembled with an amphiphilic diblock copolymer by a double-emulsion process in order to prepare giant magnetic vesicles (polymersomes) in one step and at a high throughput. It was shown in literature that such diblock copolymer W/O/W emulsion droplets can evolve into polymersomes made of a thin (nanometric) magnetic membrane through a dewetting transition of the oil phase from the aqueous internal cores usually leading to "acorn-like" structures (polymer excess) sticking to the membranes. To address this issue and greatly speed up the process, the solvent removal by evaporation was replaced by a "shearing-off" of the vesicles in a simple PDMS chip designed to exert a balance between a magnetic gradient and viscous shear. In the second example, a simple oil-in-oil emulsion chip is used to obtain regular trains of magnetic droplets that circulate inside an inductor coil producing a radio-frequency magnetic field. We evidence that the heat produced by magnetic hyperthermia can be converted into a temperature rise even at the scale of nL droplets. The results are compared to heat transfer models in two limiting cases: adiabatic vs. dissipative. The aim is to decipher the delicate puzzle about the minimum size required for a tumor "phantom" to be heated by radio-frequency hyperthermia in a general scope of anticancer therapy.