Microfluidic Devices: A Tool for Nanoparticle Synthesis and Performance Evaluation

Abstract

The use of nanoparticles (NPs) in nanomedicine holds great promise for the treatment of diseases for which conventional therapies present serious limitations. Additionally, NPs can drastically improve early diagnosis and follow-up of many disorders. However, to harness their full capabilities, they must be precisely designed, produced, and tested in relevant models. Microfluidic systems can simulate dynamic fluid flows, gradients, specific microenvironments, and multiorgan complexes, providing an efficient and cost-effective approach for both NPs synthesis and screening. Microfluidic technologies allow for the synthesis of NPs under controlled conditions, enhancing batch-to-batch reproducibility. Moreover, due to the versatility of microfluidic devices, it is possible to generate and customize endless platforms for rapid and efficient in vitro and in vivo screening of NPs’ performance. Indeed, microfluidic devices show great potential as advanced systems for small organism manipulation and immobilization. In this review, first we summarize the major microfluidic platforms that allow for controlled NPs synthesis. Next, we will discuss the most innovative microfluidic platforms that enable mimicking in vitro environments as well as give insights into organism-on-a-chip and their promising application for NPs screening. We conclude this review with a critical assessment of the current challenges and possible future directions of microfluidic systems in NPs synthesis and screening to impact the field of nanomedicine.

Synthesis of Submicron CaCO3 Particles in 3D-Printed Microfluidic Chips Supporting Advection and Diffusion Mixing

“…Microfluidic systems offer significantly higher surfaceto-volume ratios compared to conventional flask-based systems, thus resulting in better control over heat and mass transfer rates. Literature analysis shows that microfluidic synthesis outperforms flask-based synthesis in terms of controllability, monodispersity, reproducibility, reagent efficiency, and impurity minimization due to better control over nanocrystal growth processes [23,24].…”

Optimization of a tunable process for rapid production of calcium phosphate microparticles using a droplet-based microfluidic platform

“…An inherent property of all microfluidic-based methods is the reduced reagent consumption due to the small volume of fluids used for operation of microfluidic devices ( Guttenplan et al, 2021a ). Compared to bulk emulsion systems, the precise control over the fluid conditions in small volumes has rendered the droplet microfluidic-based techniques suitable for producing highly monodisperse particles ( Guttenplan et al, 2021a ; Cai et al, 2021 ; Seeto et al, 2022 ), from micro-to nano-scale ( Gimondi et al, 2023 ; Nan et al, 2024 ). This also minimizes the batch-to-batch variation in terms of particle size.…”

Microfluidics-enabled fluorinated assembly of EGCG-ligands-siTOX nanoparticles for synergetic tumor cells and exhausted t cells regulation in cancer immunotherapy

“…To achieve rapid synthesis and screening of the lead formulation, we employed a microfluidic approach as an advanced technology for the production, testing, and application of NPs, taking advantages of its ability to simulate dynamic fluid flows, gradients, and specific microenvironments. As a result, we were able to fabricate a series of LFNPs1, LFNPs2, LFNPs3, and LFNPs/siTOX complexes with high reproducibility, simple operation, and time effectiveness, in comparison to conventional methods such as the dropwise method [ 28 – 30 ]. Therefore, microfluidics is highly suitable for ensuring the controlled synthesis of NPs with consistent physicochemical properties, ultimately leading to the desired therapeutic efficacy in vivo (Fig.…”