Microfluidic-Based Synthesis of Magnetic Nanoparticles Coupled with Miniaturized NMR for Online Relaxation Studies

Abstract

Using compact desktop NMR systems for rapid characterization of relaxation properties directly after synthesis can expedite the development of functional magnetic nanoparticles. Therefore, an automated system that combines a miniaturized NMR relaxometer and a flow-based microreactor for online synthesis and characterization of magnetic iron oxide nanoparticles is constructed and tested. NMR relaxation properties are quantified online with a 0.5 T permanent magnet for measurement of transverse ( T) and longitudinal ( T) relaxation times. Nanoparticles with a primary particle size of about 25 nm are prepared by coprecipitation in a tape-based microreactor that utilizes 3D hydrodynamic flow focusing to avoid channel clogging. Cluster sizes are expeditiously optimized for maximum transverse relaxivity of 115.5 mM s. The compact process control system is an efficient tool that speeds up synthesis optimization and product characterization of magnetic nanoparticles for nanomedical, theranostic, and NMR-based biosensing applications.

Microfluidic Synthesis of Iron Oxide Nanoparticles

“…One of the main advantages to this technique is the ability to continuously produce nanoparticles, eliminating batch-to-batch inconsistencies. However, there could be variations in particle properties during long production times, which can be monitored by simple characterization techniques post synthesis, and then proper alterations can be made to correct the inconsistencies [ 67 ]. Additionally, channel fouling is a prevalent issue in many reactors, which can be overcome with channel coatings or changes in channel architecture.…”

“…A number of studies have been performed on microfluidic devices manufactured using PDMS [ 66 ], PTFE [ 67 ], and PMMA [ 52 ]. IONPs produced in these microfluidic devices exhibited core sizes of 35 nm for the PDMS-based device and a core size range of 12.3 to 24.6 nm in the PTFE-based device [ 66 , 67 ]. Another study used PTFE, silicone, and glass capillaries to manufacture a tubular microfluidic device with channel diameters of 400 µm for the glass capillaries and 820 µm for the PTFE and 3600 µm for the silicone tubing [ 68 ].…”

“…Characterization techniques have been incorporated into the process to provide instant feedback on particle characteristics. NMR has been incorporated into a microfluidic system to provide instant feedback on particle magnetic properties [ 67 ]. With this, it is easy to visualize integrating a dynamic light scattering size analyzer into a microfluidic system to obtain instant feedback on hydrodynamic size.…”

“…Higher concentrations of iron in solution means that more nucleation sites can form. It has been observed that increasing iron concentration decreased overall particle hydrodynamic diameter [ 67 ]. This concentration can be controlled by altering the initial solution or by varying the iron solution flow rate, assuming turbulent mixing is not a result.…”

Strategy for fast manufacturing of 3D hydrodynamic focusing multilayer microfluidic chips and its application for flow-based synthesis of gold nanoparticles

“…3D microfluidic structure was bonded by a lamination process using mild pressure with a roller and foils coated with an adhesive. Our strategy is to develop highly flexible plastic microreactors without masks and molds (Bemetz et al 2018). The advantage is that cleanroom requirements due to the absence of lithographic methods are eliminated.…”