On-chip microfluidic production of cell-sized liposomes

Journal Article (2018)
Author(s)

Siddharth Deshpande (TU Delft - BN/Cees Dekker Lab)

Cees Dekker (TU Delft - BN/Cees Dekker Lab)

BN/Cees Dekker Lab
DOI related publication
https://doi.org/10.1038/nprot.2017.160
More Info
expand_more
Publication Year
2018
Language
English
BN/Cees Dekker Lab
Issue number
5
Volume number
13
Pages (from-to)
856-874

Abstract

In this protocol, we describe a recently developed on-chip microfluidic method to form monodisperse, cell-sized, unilamellar, and biocompatible liposomes with excellent encapsulation efficiency. Termed octanol-assisted liposome assembly (OLAOLAOLA), it resembles bubble-blowing on a microscopic scale. Hydrodynamic flow focusing of two immiscible fluid streams (an aqueous phase and a lipid-containing 1-octanol phase) by orthogonal outer aqueous streams gives rise to double-emulsion droplets. As the lipid bilayer assembles along the interface, each emulsion droplet quickly evolves into a liposome and a 1-octanol droplet. OLAOLAOLA has several advantages as compared with other on-chip techniques, such as a very fast liposome maturation time (a few minutes), a relatively straightforward and completely on-chip setup, and a biologically relevant liposome size range (5-20 μm). Owing to the entire approach being on-chip, OLAOLAOLA enables high-throughput liposome production (typical rate of tens of Hz) using low sample volumes (~10 &mul). For prolonged on-chip experimentation, liposomes are subsequently purified by removing the 1-octanol droplets. For device fabrication, a reusable silicon template is produced in a clean room facility using electron-beam lithography followed by dry reactive ion etching, which takes ~3 h. The patterned silicon template is used to prepare polydimethylsiloxane (PDMS)-based microfluidic devices in the wet lab, followed by a crucial surface treatment; the whole process takes ~2 d. Liposomes can be produced in ~1 h and further manipulated, depending on the experimental setup. OLAOLAOLA offers an ideal microfluidic platform for diverse bottom-up biotechnology studies by enabling creation of synthetic cells, microreactors and bioactive cargo delivery systems, and also has potential as an analytical tool.

No files available

Metadata only record. There are no files for this record.