Analysis of the Diffusion Process by pH Indicator in Microfluidic Chips for Liposome Production

Abstract

In recent years, the development of nano- and micro-particles has attracted considerable interest from researchers and enterprises, because of the potential utility of such particles as drug delivery vehicles. Amongst the different techniques employed for the production of nanoparticles, microfluidic-based methods have proven to be the most effective for controlling particle size and dispersity, and for achieving high encapsulation efficiency of bioactive compounds. In this study, we specifically focus on the production of liposomes, spherical vesicles formed by a lipid bilayer encapsulating an aqueous core. The formation of liposomes in microfluidic devices is often governed by diffusive mass transfer of chemical species at the liquid interface between a solvent (i.e., alcohol) and a non-solvent (i.e., water). In this work, we developed a new approach for the analysis of mixing processes within microfluidic devices. The method relies on the use of a pH indicator, and we demonstrate its utility by characterizing the transfer of ethanol and water within two different microfluidic architectures. Our approach represents an effective route to experimentally characterize diffusion and advection processes governing the formation of vesicular/micellar systems in microfluidics, and can also be employed to validate the results of numerical modelling.

Influence of channel height on mixing efficiency and synthesis of iron oxide nanoparticles using droplet-based microfluidics

“…30 For the experimental evaluation of mixing performance, a variety of microscopic techniques with the aid of ow visualisation by pH-sensitive, coloured and uorescent dyes, have been employed. 14,31,32 Two-dimensional projection of a 3D droplet into a plane has been addressed by Fluorescence-Lifetime Imaging (FLIM) providing three-dimensional information about a tracer distribution for both, quasi-steady ows 32 and rapidly owing droplets. 33 However, a high purchasing cost signicantly hinders the widespread application of this technique.…”

Continuous flow production of size-controllable niosomes using a thermostatic microreactor

“…Solvent and no-solvent diffusion by hydrodynamic flow focusing was monitored by an adaption of a previous published methodology [32]. Briefly, a change in colour of a pH indicator dye (bromoxylenol blue) was used, since this dye exhibits a strong yellowish colour at pH below 6.0 and blue at pH above 7.6.…”

“…Some authors [19,20,32] reported a significantly increase in PDI with the increment of FRR for an identical chip configuration, but for liposomes production instead. However, our observation was in line with that of Bottaro et al [32] in a "Y"-shaped device, while Joshi et al [21] described also a reduction in PDI as FRR increase during liposome formation. No significant differences on PDI were observed for all Q T levels applied.…”

“…The efficiency of mixing under the assayed working conditions was studied following a published methodology [32]. With this method, mixing efficiency was measured through the change in colour of a pH indicator dye (bromoxylenol blue), that changed from yellow (acidic ethanolic solution containing bilayer precursors) to blue (basic aqueous phase, PBS pH= 10).…”

Surface Response Based Modeling of Liposome Characteristics in a Periodic Disturbance Mixer

“…Alternatives to such types of devices are Dean forces-based micromixers, which use curvilinear paths to induce centripetal forces, thus speeding up the mixing process [20][21][22]. Multiple micromixer designs using Dean forces have been previously proposed [19,[23][24][25][26][27], showing promising results for lipid-based nanoparticles both in terms of increased yield (by reducing the Flow Rate Ratio (FRR) required to produce nanosized particles) as well as ease of fabrication of the microfluidic devices.…”