Integrated Microfluidic System for Size-Based Selection and Trapping of Giant Vesicles

Abstract

Vesicles composed of phospholipids (liposomes) have attracted interest as artificial cell models and have been widely studied to explore lipid-lipid and lipid-protein interactions. However, the size dispersity of liposomes prepared by conventional methods was a major problem that inhibited their use in high-throughput analyses based on monodisperse liposomes. In this study, we developed an integrative microfluidic device that enables both the size-based selection and trapping of liposomes. This device consists of hydrodynamic selection and trapping channels in series, which made it possible to successfully produce an array of more than 60 monodisperse liposomes from a polydisperse liposome suspension with a narrow size distribution (the coefficient of variation was less than 12%). We successfully observed a size-dependent response of the liposomes to sequential osmotic stimuli, which had not clarified so far, by using this device. Our device will be a powerful tool to facilitate the statistical analysis of liposome dynamics.

Microfluidic Handling and Analysis of Giant Vesicles for Use as Artificial Cells: A Review

“…[28,43,78,79] For the bottom-up creation of artificial cells, having a monodisperse population may be advantageous for making repeat observations of morphological changes or to control the rates of encapsulated enzymatic reactions. [28,43,78,79] For the bottom-up creation of artificial cells, having a monodisperse population may be advantageous for making repeat observations of morphological changes or to control the rates of encapsulated enzymatic reactions.…”

“…[28,43,78,79] For the bottom-up creation of artificial cells, having a monodisperse population may be advantageous for making repeat observations of morphological changes or to control the rates of encapsulated enzymatic reactions. [29,78] Storslett and Muller showed that inertial focusing can be used to sort different vesicle populations into different outlet channels. On-chip size selection can either be achieved using trapping posts and changing the height of microchannels [28] or by filtering the GUVs based on their behavior in different flows.…”

“…Few works have highlighted the fact that microfluidic devices can be used to size select giant vesicles from a very polydisperse initial population (i.e., from electroformation or gentle hydration techniques). [28,43,78,79] For the bottom-up creation of artificial cells, having a monodisperse population may be advantageous for making repeat observations of morphological changes or to control the rates of encapsulated enzymatic reactions. Size selection does away with the need to produce monodisperse vesicles using techniques like microfluidic double-emulsion templating which can be undesirable due to fabrication complexities and residual oil in the lipid bilayer.…”

“…On-chip size selection can either be achieved using trapping posts and changing the height of microchannels [28] or by filtering the GUVs based on their behavior in different flows. [29,78] Storslett and Muller showed that inertial focusing can be used to sort different vesicle populations into different outlet channels. [29] In the same study, vesicle sorting was demonstrated by size exclusion using narrow microchannels.…”

“…[96] So far, the focus has been on developing microfluidic technologies for controllably trapping one [28,30,62,76,78] or even two [87] GUVs at a defined location. [96] So far, the focus has been on developing microfluidic technologies for controllably trapping one [28,30,62,76,78] or even two [87] GUVs at a defined location.…”