Continuous-flow reactors for large-scale production of nanoparticles

Abstract

Nowadays, nanoparticles are involved in an enormous amount of applications, including energy-saving and material science, anti-cancer and antimicrobial therapies, drug delivery and the treatment of infectious and parasitic diseases. However, they are often expensive to purchase or challenging to produce. Specifically, achieving fine control over their size and/or shape, by managing the correct stoichiometry of the reaction, is a crucial task to accomplish. This challenge becomes even more demanding for researchers working towards large-scale production processes. Continuous-flow reactors have been previously used to address those issues. However, their manufacturing, particularly for devices containing nano- and micro-sized channels, requires not only expensive materials but also laborious protocols, which must be performed within exclusive facilities under controlled environmental conditions (such as cleanrooms). Identifying an economically favourable and simple-to-perform translation from batchsynthesis to large-scale flow-production of size- and shape-controlled nanomaterials, was the main aim of the present PhD project. Particularly, cost-effective flow-reactors were conceived and manufactured using 3D printing, either directly or via the soft-lithographic approach. The latter method was the most adopted, and allowed the realisation of the here called 3D printed replica mould casted (3DP-RMC) flow-reactors. The high-resolution Objet Connex 350 and the fused deposition modeling (FDM) Ultimaker 2+ 3D printers were tested, and their moulds were characterised and compared. The research led to the development of novel methods and protocols such as the pump-free 3D printed reactor-in-a-centrifuge (RIAC), light-activated flow-reactors, the thermally-controlled flow-synthesis and the bonding procedure via pressure-sensitive adhesive tape. The effectiveness and reliability of the conceived reactors were proven through the synthesis of representative inorganic and organic nanoparticles. From the inorganic nanomaterials’ perspective, silver nanoparticles (AgNPs) were selected as largely applied in numerous fields, ranging from drug delivery to antibacterial and sensing, due to the combined effects of the material itself and their shape- and size-dependent optical properties. Although silver nanospheres (AgNSs) were produced, due to a parallel collaboration with the Defence Science and Technology Laboratory (Dstl), particular attention was focused on the batch- to flow-synthesis translation of near infrared (NIR) absorbing silver nanoprism (AgNPrs). The low reproducibility of the batch method was demonstrated as well as the improvements made on the customised flow-reactors. For the latter, the UV-vis and TEM characterisations demonstrated the production of AgNPrs with a consistent wavelength absorbance maxima (WAmax) of ̴ 870 nm and a ̴ 30% improved SD. Moreover, regarding the large-scale goal, AgNPrs were obtained at the operating flor-rate of tens of mL/min, which is notably higher when compared to the previously published flow-studies, which operated at more than 5 mL/hour. Manufacturing improvements were made and reactors were generally designed and tested, based on the application, to achieve the desired control over the mixing regimes, chemical ratios and stoichiometry, as well as to minimise production costs. In order to validate their feasibility for the production of organic nanomaterials, and to demonstrate their robustness and reliability, nanovesicles such as liposomes and niosomes were also produced. RIAC and 3DP-RMC bonded on pressure-sensitive adhesive tape were able to produce silver nanospheres with a WAmax of 404 and 398 nm respectively, and liposomes having a diameter < 250 nm. The possibility of drastically simplifying the manufacturing protocols and reducing the production cost of continuous-flow devices was highlighted by the pressure-sensitive adhesive tape solution, that allows manufacturing flow-reactors at <£5 per device and a fabrication time <24 hours. Differently, the optical fibre embedded devices were used for the first photo-assisted flowbioproduction of silver nanospheres (AgNSs) by bacteria. Finally, by using high-resolution 3D printed moulds, reactors bonded on glass were demonstrated to be sealed even when operating submerged into a thermal bath at 50 °C

More information

Identifiers

ORCID for Xunli Zhang: orcid.org/0000-0002-4375-1571

Catalogue record

Export record