Investigation into the Use of Microfluidics in the Manufacture of Metallic Gold-Coated Iron Oxide Hybrid Nanoparticles.

Adeolu Oluwasanmi,Clare Hoskins,Humphrey H. P. Yiu,Yvonne Perrie,Ernest Man,Anthony Curtis

doi:10.3390/nano11112976

Adeolu Oluwasanmi, Clare Hoskins + Show 4 more

Open Access

https://doi.org/10.3390/nano11112976

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Abstract

Hybrid iron oxide-gold nanoparticles are of increasing interest for applications in nanomedicine, photonics, energy storage, etc. However, they are often difficult to synthesise without experience or ‘know-how’. Additionally, standard protocols do not allow for scale up, and this is significantly hindering their future potential. In this study, we seek to determine whether microfluidics could be used as a new manufacturing process to reliably produce hybrid nanoparticles with the line of sight to their continuous manufacture and scaleup. Using a Precision Nano NanoAssemblr Benchtop® system, we were able to perform the intermediate coating steps required in order to construct hybrid nanoparticles around 60 nm in size with similar chemical and physical properties to those synthesised in the laboratory using standard processes, with Fe/Au ratios of 1:0.6 (standard) and 1:0.7 (microfluidics), indicating that the process was suitable for their manufacture with optimisation required in order to configure a continuous manufacturing plant.

Highlights

Whilst many nanoparticles have shown excellent potential in laboratory testing for sectors such as energy [1], agriculture [2] or healthcare [3], the ability to reliably and repeatably scale up their manufacture has hindered their ability to be marketed or proceed further down their developmental pipeline, for clinical application [4,5,6]
Gold-coated iron oxide hybrids are synthesised in small batches as a benchtop multistep synthesis in the laboratory (Figure 1), which is monitored via measurement of zeta potential at each point of the synthesis to track progress
One major challenge hindering the ability of these exciting Hybrid iron oxide-gold nanoparticles (HNPs) platforms as diagnostic agents, drug delivery vehicles and theranostic applications, for progressing further down the pathway towards clinical translation, is their ability to be manufactured at a large scale

Summary

Introduction

Whilst many nanoparticles have shown excellent potential in laboratory testing for sectors such as energy [1], agriculture [2] or healthcare [3], the ability to reliably and repeatably scale up their manufacture has hindered their ability to be marketed or proceed further down their developmental pipeline, for clinical application [4,5,6]. We seek to determine whether the chemical synthesis precipitation-based reactions may be prone to deposition and clogging within flow-based of core-shell gold-coated oxide particles is feasiblethe using microfluidics, systems. Ylenimine) intermediate layer is added in order to help maintain the integrity of the physThe process of HNP synthesis usually relies on high temperatures and lengthy reaction ical properties of both the iron oxide and gold shell for later applications. The process of HNP synthesis usually relies on high temperatures and lengthy reacwhether the superior mixing of microfluidics could be used to more efficiently produce tion durations for crystal formation. This investigation will allow us to elucidate these. All studies will be compared to the current benchtop synthetic procedure for HNP formation

Hybrid Nanoparticle Synthesis

Microfluidic Hybrid Nanoparticle Synthesis

Synthesis of Fe3 O4

PEI Coating of Fe3 O4

Gold Seeding of Fe3 O4 -PEI

Gold Coating of Fe3 O4 -PEI-Au Seeds

Photon Correlation Spectroscopy

Inductively Coupled Plasma—Optical Emission Spectroscopy

Transmission Electron Microscopy

Results and Discussion

Images

Method