Modular Manufacturing Platform for Continuous Synthesis and Analysis of Versatile Nanomaterials

Abstract

Nanoparticular materials have a great potential in various fields including technical and biomedical applications; to meet the specific requirements, a good control over the particle characteristics is mandatory. Addressing this, a modular system for the automated and continuous synthesis, workup, and analysis of a broad range of nanoparticles was developed. Application examples of inorganic (silica) and organic (polymersomes, niosomes) nanoparticles demonstrate the versatility of the production platform. Modules for downstream processing via a falling‐film microreactor or tangential flow filtration are presented. The hydrodynamic size as a key parameter is acquired in real time, with an inline dynamic light scattering device. All modules are controlled and operated by a process control system.

Flow Chemistry in Contemporary Chemical Sciences: A Real Variety of Its Applications

“…For instance, in flow synthesis systems requiring minimal manual intervention, which were designed for the synthesis of a drug known as imatinib, a flow-through UV detector was used to determine when the reaction mixture exited the system in order to fractionate the reactor output for the off-line LC/MS analysis [201]. In the flow synthesis of fluorescent CdS nanoparticles in a microfluidic reactor, an in-line spectrometer to monitor the fluorescence spectra was employed [305], while, in a multi-stage flow synthesis of silica and two types of organic nanoparticles, in-line dynamic light scattering was used for real-time monitoring of the size of the obtained nanoparticles [306]. Numerous applications were reported for the use of infrared spectroscopy in real-time monitoring in flow synthesis systems, mostly using the so-called attenuated total reflection technique (ATR).…”

Non-fouling flow reactors for nanomaterial synthesis

“…The progress of flow chemistry for nanoparticle syntheses during the last decade has been remarkable as the field transitioned from proof of principle studies 10 to screening 11,12 and fully automated synthesis platforms [13][14][15] as well as large scale production. [16][17][18][19] The growing interest in robust nanomaterial flow syntheses of different material classes (from lipids to metals) requiring different synthetic routes, as well as the various flow chemistry applications (from discovery to production), resulted in a great diversity of flow reactors. This "flow reactor jungle" comprises microchip silicon and glass reactors, capillary-based systems using standard tubing and connectors, stainless steel tube and plate reactors, and many more.…”

Complex Structures Made Simple – Continuous Flow Production of Core Cross‐Linked Polymeric Micelles for Paclitaxel Pro‐Drug‐Delivery

“…In the slit-interdigital micromixer (SIMM), multilamination and geometric flow focusing lead to thin fluid lamellae and high flow velocities. [51,52] The resulting short mixing times (ms-range) in interdigital micromixers can thus be used to control selfassembly kinetically, giving access to nonequilibrium structures as reported for micelles and disc-like structures from vesicle forming polymers by Thiermann et al [46,49,53] Although microfluidics are an established technique for LNPs in nucleic acid delivery, [42,46,[54][55][56][57][58][59] a complete setup for the continuous flow production of CCPMs including online purification has not yet been realized. The combination of self-assembly, core cross-linking and purification by this methodology is a highly desirable feature to enable larger-scale production and provide access to CCPM libraries for screening of drugs and combination therapies.…”