Abstract
A continuous manufacturing platform was developed for the synthesis of aqueous colloidal 10–20 nm gold nanoparticles (Au NPs) in a flow reactor using chloroauric acid, sodium citrate and citric acid at 95 oC and 2.3 bar(a) pressure. The use of a two-phase flow system – using heptane as the continuous phase – prevented fouling on the reactor walls, while improving the residence time distribution. Continuous syntheses for up to 2 h demonstrated its potential application for continuous manufacturing, while live quality control was established using online UV-Vis photospectrometry that monitored the particle size and process yield. The synthesis was stable and reproducible over time for gold precursor concentration above 0.23 mM (after mixing), resulting in average particle size between 12 and 15 nm. A hydrophobic membrane separator provided successful separation of the aqueous and organic phases and collection of colloidal Au NPs in flow. Process yield increased at higher inlet flow rates (from 70 % to almost 100 %), due to lower residence time of the colloidal solution in the separator resulting in less fouling in the PTFE membrane. This study addresses the challenges for the translation of the synthesis from batch to flow and provides tools for the development of a continuous manufacturing platform for gold nanoparticles.Graphical abstract
Highlights
Highlights A continuous segmented flow reactor for gold nanoparticle synthesis has been developed. Continuous phase separation and online analysis for nanoparticle size and yield determination have been implemented. The platform was used to produce nanoparticles with targeted size in the 10–20 nm range.The unique properties of gold nanoparticles (Au NPs) have instigated research in their biomedical applications [1], drug delivery [2] and antimicrobial applications [3]
Nanoparticle deposition can occur on the reactor walls in the absence of a hydrophobic film separating the aqueous phase from the PTFE material [7]
The analysis showed that their values were very small (Ca < 0.0001, Weber number (We) < 0.001,Bond number (Bo) ≈ 0.01), indicating that the interfacial tension forces were dominant over the viscous, inertial and gravitational forces [27]
Summary
The unique properties of gold nanoparticles (Au NPs) have instigated research in their biomedical applications [1], drug delivery [2] and antimicrobial applications [3]. Wagner and Köhler [6] used a continuous flow microreactor for the reduction of HAuCl4 with ascorbic acid for the synthesis of 5–50 nm Au NPs capped with polyvinylpyrrolidone (PVP). They identified that during the process there was particle deposition (fouling) on the reactor walls, affecting the particle quality. Huang et al [7] examined the
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