Continuous citrate‐capped gold nanoparticle synthesis in a two‐phase flow reactor

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

Importance of Monitoring the Synthesis of Light‐Interacting Nanoparticles – A Review on In Situ, Ex Situ, and Online Time‐Resolved Studies

“…Although a number of studies in the literature clearly present the differences in the physical properties (mainly in terms of size distribution) of the nanomaterials during batch and flow syntheses, [90,289,311] only a fraction of studies properly assessed the effect of radial and axial mixing in microreactors. When done, the potential diffusion limitations are tackled using biphasic systems (to promote Taylor flow) [192,342] or 3D microreactor configurations (to promote Lagrangian turbulence, Dean vortices, or similar). [299,310] It is noteworthy, that only the use of in situ characterization in well-designed flow reactors can enable the real monitoring and understanding of the early stages of nanoparticle formation, especially during fast syntheses (few seconds to reach completion, and nucleation below ≈100 ms) in a reproducible and reliable manner.…”

A versatile non-fouling multi-step flow reactor platform: demonstration for partial oxidation synthesis of iron oxide nanoparticles

“…The difficulty of feeding new reagent solution to the reactive phase after segmentation, limits flow syntheses using liquid-liquid segmentation to simple synthetic protocols with a single reagent addition step. In some cases this limitation can be circumvented by providing all reagents before segmentation (possible if fouling is not expected/is minimal before segmentation) [29][30][31] or reagent mixing where segmentation happens. [32][33][34][35][36] Nevertheless, full flexibility to translate nanoparticle synthesis into flow requires novel non-fouling flow reactors facilitating multiple reagent addition steps when/wherever needed.…”

Simple Setup Miniaturization with Multiple Benefits for Green Chemistry in Nanoparticle Synthesis

“…Consequently, the controlled synthesis of NMs has been increasingly addressed as a key component of green chemistry. − The need for protocols generating less waste and increasing safety has been emphasized. , Selection of solvents and reactants is often focused upon, and the use of microwaves or ultrasound if considered more energy efficient . The development of setups such as flow (micro)­reactors is also useful to minimize waste and simplify NM synthesis. − However, “despite these advantages, microfluidic systems have yet to be extensively adopted by the colloidal nanomaterial community” . The above strategies often require specific equipment and expertise, which may account for their relatively limited implementation.…”