Microfluidics for Multiphase Mixing and Liposomal Encapsulation of Nanobioconjugates: Passive vs. Acoustic Systems

Abstract

One of the main routes to ensure that biomolecules or bioactive agents remain active as they are incorporated into products with applications in different industries is by their encapsulation. Liposomes are attractive platforms for encapsulation due to their ease of synthesis and manipulation and the potential to fuse with cell membranes when they are intended for drug delivery applications. We propose encapsulating our recently developed cell-penetrating nanobioconjugates based on magnetite interfaced with translocating proteins and peptides with the purpose of potentiating their cell internalization capabilities even further. To prepare the encapsulates (also known as magnetoliposomes (MLPs)), we introduced a low-cost microfluidic device equipped with a serpentine microchannel to favor the interaction between the liposomes and the nanobioconjugates. The encapsulation performance of the device, operated either passively or in the presence of ultrasound, was evaluated both in silico and experimentally. The in silico analysis was implemented through multiphysics simulations with the software COMSOL Multiphysics 5.5® (COMSOL Inc., Stockholm, Sweden) via both a Eulerian model and a transport of diluted species model. The encapsulation efficiency was determined experimentally, aided by spectrofluorimetry. Encapsulation efficiencies obtained experimentally and in silico approached 80% for the highest flow rate ratios (FRRs). Compared with the passive mixer, the in silico results of the device under acoustic waves led to higher discrepancies with respect to those obtained experimentally. This was attributed to the complexity of the process in such a situation. The obtained MLPs demonstrated successful encapsulation of the nanobioconjugates by both methods with a 36% reduction in size for the ones obtained in the presence of ultrasound. These findings suggest that the proposed serpentine micromixers are well suited to produce MLPs very efficiently and with homogeneous key physichochemical properties.

Strategies for targeted gene delivery using lipid nanoparticles and cell-derived nanovesicles

“…With techniques like laser etching and photolithography, it is further possible to reduce the microuidic chamber sizes. [36][37][38][39][40] By tuning the ow and mixing rate of the lipid and aqueous solutions in a double spiral micromixer, researchers were able to change the rigidity of the nanovesicles. 41 Furthermore, some of the microuidic-based lipid nanovesicle assembly lines could handle around 1200 ml per hour, indicating a high throughput process.…”

A review on microfluidic-assisted nanoparticle synthesis, and their applications using multiscale simulation methods

“…Organic/inorganic hybrid NPs combine organic materials such as lipid or polymer NPs with metal, metal oxide, or semiconductor materials to take advantage of their unique electrical, optical, and magnetic properties. For example, magnetoliposomes [128] consist of a magnetite NPs encapsulated in liposomes for applications in molecule separation and targeted drug delivery. Other examples include zeolitic imidazolate framework NPs (metal organic framework (MOF)) [129], and gold (core)-polystyrene (shell) NPs [130], in addition to numerous organic/inorganic core-shell combinations [131].…”

“…Overall, sonication reduced particle size from 150 to 50 nm, while 120 nm was the minimum diameter reached without sonication. Giraldo et al [128] synthesized magnetoliposomes (MLP), which combine liposomes and nanostructured magnetic materials (magnetite) for drug delivery applications. A laser engraved PMMA microchannel was fabricated with a serpentine design.…”

Numerical study of passive branches micromixer based on split-and-recombination and vortex mixing

“…For decrease mixing time and channel length, various designs of micromixer have been developed, it can be classified in the literature into two categories-active and passive micromixers (Chiarot et al 2004;Jeong et al 2010). Active micromixers require external energy input to enhance mixing process, including electrokinetic, acoustic, pulsating flow and magnetic field (Abdolahzadeh et al 2022;Barz et al 2011;Giraldo et al 2021;Li and Kim 2017). These have highly efficiently mixing rate, but require peripheral devices and more complex manufacturing processes.…”