Liposomes on chip

We aim to establish an artificial life cycle of liposomes specifically exhibiting two fundamental characteristics of living systems: growth and division. We intend to do this on a microfluidic chip, where the liposomes are produced, grown, and finally divided, whereupon the cycle is repeated.

We recently developed a novel microfluidic method, Octanol-assisted Liposome Assembly (OLA), which produces cell-sized (5–20 µm), monodispersed, unilamellar liposomes with an excellent encapsulation efficiency (see here). OLA is a process akin to bubble-blowing which uses 1-octanol as the lipid-carrying solvent, and results in spontaneous formation of liposomes, along with the waste product, 1-octanol droplets. We then perform on-chip density-based separation of droplets, in order to get a pure yield of liposomes. These liposomes are further manipulated according to the need, such as immobilization using microfluidic traps or shape manipulation by squeezing them into narrow confinements.

We aim to bring about liposomal membrane growth by recruitment of lipids from the external environment. One way of doing this would be membrane fusion of small unilamellar vesicles to mother liposomes, facilitated by increasing the membrane tension through osmotic stress. By colliding the liposomes against well-defined microfluidic obstacles, we can split the liposomes into two daughter liposomes. This is a novel way to divide the liposomes using external physical forces. We are currently quantifying the efficiency, division symmetry, and the leakage involved in the process.

Integrating these three modules to establish a continuous life cycle of vesicles is a future challenge. This will provide a dynamic system of growing-and-dividing liposomes in an evolutionary cycle which can be used as a fundamental tool to apply the bottom-up strategy to synthetic cells.