Scientists at the University of Tokyo have developed a systematic method to produce identical lipid-coated microspheres that can hold liquid, an important step toward creating artificial cells or nanovesicles for drug delivery. The technology overcomes the difficulty of producing uniform spheres having exactly one lipid bilayer and the tricky issue of loading the vesicles with a premixed liquid substance.
Chemistry World News reports:
The team’s high-throughout production method uses a microfluidic device consisting of a main channel lined with small chambers. To prepare the device, it is first filled with an aqueous solution containing the material that will make up the vesicles’ contents. Oil is then flowed through the device’s main channel. This washes the aqueous solution out of the channel, trapping the water in the chambers where a monolayer forms at the interface of the oil and water. The aqueous solution then re-enters the main channel, replacing the oil and pushing some of it down into the top of each of the chambers. A layer of lipid forms here, squashed between the two aqueous layers, with a monolayer at both the ‘water’-oil interfaces.
Next, a continuous stream of another aqueous solution is pushed through the main channel, and a gentle flow of the original aqueous solution allowed to enter from bottom of each of the chambers. The flow across the chamber entrance combined with the gentle flow upwards from bottom of the chamber causes the lipid layer to thin out, and the two monolayers to form one bilayer. The shear force combined with the upwards flow of aqueous solution means the lipid bilayer is pulled/pushed up into the fast flowing stream of aqueous solution in the device’s main channel. The shear force of the flow on the deformed bilayer eventually leads to a vesicle being pulled off from the leading edge of the bilayer. This process then continues, releasing ‘perfectly’ sized and shaped vesicles at regular intervals (see image and video).
One bilayer produces 50 to 100 vesicles, and with multiple chambers in the main channel each device can produce thousands of vesicles at a rate of several hundred vesicles per minute. The device currently only works for a limited period (until the lipid bilayer runs out), but the researchers say that they should be able to scale up the process by making the lipid layer at the top of each chamber thick enough to make several thousand vesicles per chamber.
Here’s a video of vesicles budding off in a flow microreactor:
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