A new microfluidic platform for the highly reproducible preparation of non-viral gene delivery complexes

Protopapa, Giovanni; Bono, Nina; Visone, Roberta; D'Alessandro, Fabio; Rasponi, Marco; Candiani, Gabriele

doi:10.1039/d2lc00744d

Cited by 5 publications

(6 citation statements)

References 64 publications

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“…7). 45 Here, several herringbone mixers are assembled on one chip, enabling the production of seven solutions with different N/P ratios in one process.…”

Section: Single-flow Devices For the Preparation Of Drug-loaded Nanop...mentioning

confidence: 99%

“…This is, of course, a far cry from the myriad of cationic polymer structures that have already been tested for nucleic acid delivery and highlights that the field of flow assembly is only emerging. 5 The set-up appears fairly simple as two aqueous solutions are mixed either using turbulent flow such as in a microfluidic cartridge that contains herringbone grooves, 45 or by laminar flow in a microfluidic hydrodynamic focusing device, 47 which can have an advanced design and include single or double meandering channels. 71 The latter publication also discusses in detail the intricacies of flow assembly such as the pump pressure profile and the design of a system that can be used for scaling up.…”

Section: Assembly Of Water-soluble Systemsmentioning

confidence: 99%

“…79 For example, using a chaotic serial dilution generator (SDG), which is a stand-alone microfluidic cartridge that was designed to control the features of nanoparticles, smaller sized PEI-DNA polyplexes (145 nm) with lower dispersities (PDI < 0.2) were obtained compared with bulk mixing (176 nm, PDI > 0.5 at N/P ratio of 40). 45 Using the same materials, Koh et al employed a different microfluidic device, a standalone microfluidic cartridge (a chaotic SDG), to obtain Fig. 9.…”

Section: Comparison Of Bulk Mixing With Flow Mixingmentioning

confidence: 99%

“…Although higher N/P ratios usually leads to smaller sizes and lower PDIs, the authors observed an optimum at a N/P ratio of 50. 45…”

Section: N/p Ratiomentioning

confidence: 99%

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Flow-based assembly of nucleic acid-loaded polymer nanoparticles

Xu,

McCarrol,

Stenzel

2023

Aust. J. Chem.

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Since the development of messenger RNA (mRNA)-based SARS-CoV-2 (COVID-19) vaccines, there is increased public awareness of the importance of nanoparticles, in this case lipid nanoparticles, to ensure safe delivery of an active compound. To ensure the formation of high-quality nanoparticles with reproducible results, these lipid nanoparticles are assembled with the nucleic acid drug using flow-based devices. Although flow assembly using lipid nanoparticles for nucleic acid delivery is well described in the literature, only a few examples use polymers. This is surprising because the field of polymers for nucleic acid delivery is substantial as hundreds of polymers for nucleic acid delivery have been reported in the literature. In this review, we discuss several aspects of flow-based assembly of nucleic acid-loaded polymer nanoparticles. Initially, we introduce the concept of chip-based or capillary-based systems that can be either used as single-phase or multiphase systems. Initially, researchers have to choose the type of mixing, which can be active or passive. The type of flow, laminar or turbulent, also significantly affects the quality of the nanoparticles. We then present the type of polymers that have so far been assembled with mRNA, small interfering RNA (siRNA) or plasmid DNA (pDNA) using flow devices. We discuss effects such as flow rate, concentration and polymer lengths on the outcome. To conclude, we highlight how flow assembly is an excellent way to generate well-defined nanoparticles including polyplexes in a reproducible manner.

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“…7). 45 Here, several herringbone mixers are assembled on one chip, enabling the production of seven solutions with different N/P ratios in one process.…”

Section: Single-flow Devices For the Preparation Of Drug-loaded Nanop...mentioning

confidence: 99%

Section: Assembly Of Water-soluble Systemsmentioning

confidence: 99%

Section: Comparison Of Bulk Mixing With Flow Mixingmentioning

confidence: 99%

“…Although higher N/P ratios usually leads to smaller sizes and lower PDIs, the authors observed an optimum at a N/P ratio of 50. 45…”

Section: N/p Ratiomentioning

confidence: 99%

See 2 more Smart Citations

Flow-based assembly of nucleic acid-loaded polymer nanoparticles

Xu,

McCarrol,

Stenzel

2023

Aust. J. Chem.

View full text Add to dashboard Cite

show abstract

“…According to the different methods of mixing, microfluidic mixers can be divided into two types: passive mixing and active mixing. For passive mixing digital microfluidic platforms that require additional auxiliary platforms, pumps [ 10 , 11 ], valves [ 12 ], and other devices are typically required to implement the hybrid function. One of the simplest methods is to insert an obstacle into the flow channel, the addition of which causes the liquid in the flow channel to create vortices around the barriers [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

EWOD Chip with Micro-Barrier Electrode for Simultaneous Enhanced Mixing during Transportation

Gao

Rui

Zeng

et al. 2023

Sensors

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Digital microfluidic platforms have been extensively studied in biology. However, achieving efficient mixing of macromolecules in microscale, low Reynolds number fluids remains a major challenge. To address this challenge, this study presents a novel design solution based on dielectric electro-wetting (EWOD) by optimizing the geometry of the transport electrode. The new design integrates micro-barriers on the electrodes to generate vortex currents that promote mixing during droplet transport. This design solution requires only two activation signals, minimizing the number of pins required. The mixing performance of the new design was evaluated by analyzing the degree of mixing inside the droplet and quantifying the motion of the internal particles. In addition, the rapid mixing capability of the new platform was demonstrated by successfully mixing the sorbitol solution with the detection solution and detecting the resulting reaction products. The experimental results show that the transfer electrode with a micro-barrier enables rapid mixing of liquids with a six-fold increase in mixing efficiency, making it ideal for the development of EWOD devices.

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Highly branched poly β-amino ester/CpG-depleted CFTR plasmid nanoparticles for non-viral gene therapy in lung cystic fibrosis disease

Qiu,

Manzanares,

et al. 2024

Molecular Therapy - Methods & Clinical Development

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A new microfluidic platform for the highly reproducible preparation of non-viral gene delivery complexes

Abstract: Transfection describes the delivery of exogenous nucleic acids (NAs) to cells utilizing non-viral means. In the last decades, scientists have been doing their utmost to design ever more effective transfection...

Cited by 5 publications

References 64 publications

Flow-based assembly of nucleic acid-loaded polymer nanoparticles

Flow-based assembly of nucleic acid-loaded polymer nanoparticles

EWOD Chip with Micro-Barrier Electrode for Simultaneous Enhanced Mixing during Transportation

Highly branched poly β-amino ester/CpG-depleted CFTR plasmid nanoparticles for non-viral gene therapy in lung cystic fibrosis disease

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