JETS of fluid propelled by the collapse of microscopic bubbles could deliver drugs directly into cancer cells, if an idea from a team of engineers pays off. They have made the bubbles project a fine jet that is powerful enough to puncture the cell wall and enter the cell.
Applying a pulse of heat or ultrasound to a fluid can produce bubbles that initially expand rapidly, before collapsing suddenly when the pulse ends. Pei Zhong and his team at Duke University in Durham, North Carolina, knew that the collapsing bubbles send a pressure wave through the surrounding fluid, and that oscillations at the surface of the bubble can generate a needle-like jet. The problem is predicting where the jet will go, and how powerful it will be.
"Previously, there has been little control in jetting direction, and it has been hard to control the strength of the jet," Zhong says. Now the team has shown that when pairs of bubbles collapse in close proximity, they interact in a predictable way.
Using successive pulses from two lasers, one with a wavelength of 1064 nanometres and the other radiating at 532 nanometres, the team rapidly heated a sample of fluid containing the dye trypan blue. The first pulse produced a bubble of vapour 50 micrometres across, and the second produced another bubble close to the first. As the bubbles cooled and contracted, their surfaces began to oscillate, creating vortices in the surrounding fluid. The interaction between neighbouring bubbles caused them to collapse, creating a pair of jets shooting out in opposite directions. This should provide the degree of control necessary for a targeted drug delivery system, Zhong says.
The size of the bubble is crucial, as it dictates the size of the jet, Zhong says. "We want to produce a tiny jet that can penetrate a cell without killing it," he adds.
Zhong and his team tested their bubble needle on cells obtained from a rat tumour. High-speed photography showed that the microbubble pair could be made to collapse in such a way that the jet of blue dye created a hole between 0.2 and 2 micrometres across - allowing the jet of liquid to enter without instantly destroying the cell (Physical Review Letters, DOI: 10.1103/PhysRevLett.105.078101). This shows the jets are suitable for targeting drugs at cells within the body, Zhong says.
He says that it should be possible to use microbubble pairs generated by ultrasound rather than lasers as a clinical drug-delivery system.
Not everyone is convinced that the system will work in a clinical setting, however. In the presence of biological tissues, the oscillating bubbles may be less stable than in the test solution, making it difficult to deliver drugs with any accuracy, says Constantin Coussios, a biomedical engineer at the University of Oxford.
