Researchers in Canada have developed a technique for making microscopic capsules out of biopolymers. The method, based on a microfluidic approach, can create capsules smaller than previously possible, with unprecedented control over size.

Microcapsules made from biopolymers are important for a number of applications, ranging from drug delivery and cosmetic preparations to the delivery of cells to the body for therapeutic purposes.

The team, based at the University of Toronto, made the capsules in a two-stage process on a microfluidic chip. First, an aqueous solution of biopolymer, such as alginate or carboxymethylcellulose, was passed through a narrow orifice into an organic phase to create droplets of the polymer solution. The size of these droplets - and hence the final capsule - was controlled relatively easily, according to the researchers, by altering the flow rates of the liquid and the size of the orifice. The droplets were passed into a microchannel where the droplets gelled. A cationic cross-linking agent was dissolved within the organic phase. The cation preferentially moved from the organic phase into the droplets where cross-linking took place, which created a microgel capsule.

The pressure-driven microfluidic system drove the microcapsules into a phase that contained no cross-linking reagent, quenching the process of gelation.

'By controlling the amount of time that the droplets remain on the microfluidic chip or by changing the concentration of the cross-linking agent, it is possible to exert tight control over the extent of cross-linking and hence the thickness of the shell of the capsule,' Eugenia Kumacheva, a member of the Toronto team, told Chemistry World. 'My collaborator Gilbert Walker has demonstrated that shell compliance is in the desired range. Also we can make much smaller capsules than has previously been possible - down to around 30 micrometres in diameter, which is small enough to encapsulate a single cell. The size distribution of the microcapsules is extremely narrow.'

The researchers have shown it is possible to encapsulate cell-sized polystyrene beads by mixing them with the initial biopolymer solution before producing the droplets. They are now experimenting with stem cells. 'There are many situations where biologists want to study individual cells in isolation, and this provides one way of achieving this,' said Kumacheva. 

Rustem Ismagilov, of the University of Chicago, US, said that Kumacheva's approach of using droplets to fabricate biopolymer capsules of controlled size, shape and composition was 'very clever' and predicted that it would find numerous applications. 

Simon Hadlington