Table 1.

Advantages, disadvantages/challenges, stage of development and potential impact of microfluidic systems on different steps in the clinical translation of nanoparticles.

	Advantages	Disadvantages/challenges	Stage of development	Potential impact
Synthesis	Tunable nanoparticle size Narrower size distribution Reproducible synthesis Potential for high-throughput synthesis and optimization of nanoparticles	Solvent and high-temperature incompatibility for low-cost polydimethylsiloxane microchannels Higher costs and complexities in the fabrication of glass and silicon microdevices	*****	Rapid combinatorial, controlled and reproducible synthesis of libraries of distinct nanoparticles for a specific application, and/or reference nanoparticles for toxicology studies
Characterization	Label-free characterization Potential for feedback control and real-time nanoparticle optimization	Current methods are not applicable to all classes of nanoparticles Not all properties can be characterized, such as drug encapsulation and release, and signal-to-noise ratio	*	In-line rapid characterization and optimization of nanoparticles
In vitro	Biological conditions closer to in vivo microenvironments Potential for high-throughout screening of a large number of nanoparticles at different concentrations	Higher costs and complexities in the fabrication and operation compared with well plates Might not be reusable and if reusable, it would be difficult to keep sterile	****	High-throughput studies of nanoparticle toxicity, efficacy, tumour penetration and organ distribution, using ‘organ-on- a-chip’ systems
In vivo	Large number of organisms could be used for a single measurement High-throughput evaluation of toxicity for a large number of nanoparticles	Lack of methods to translate data from small-scale organisms to other species Pharmacokinetics or biodistribution cannot be determined	**	Real-time tracking of the distribution or toxicity of nanoparticles on small-scale organisms
Large-scale synthesis	Continuous synthesis Bench-scale to clinical-scale reproducibility Parallelization allows for tuning scale of production	Difficult to build systems at low-cost that are comparable to a batch reactor able to prepare grams or kilograms of nanoparticles	***	Synthesis of nanoparticles for human administration using stackable parallel microfluidic units

^(*****)Rank: Most advanced in development

^(*)to least advanced in development, based on the amount of research carried out on each category, as well as the potential ease of adoption by industry.