The Times — November 13, 2019

By Rhys Blakely, Science Correspondent

Scientists have developed a means of using sound waves to track and manoeuvre tiny parcels of drugs to precise locations inside the body.

The technique could be used to ferry powerfully toxic cancer treatments to tumour sites, avoiding damage to surrounding tissues and dramatically reducing the amount of the drug to which the patient is exposed, researchers said.

It might also be used in gene therapies, where genetic material must reach and infiltrate a small target group of cells. At present once a drug is injected doctors typically have little control. The accuracy of delivery can be judged by taking tissue samples from a patient. Alternatively, radioactive materials can be used to chart the progress of some medicines inside the body.

“We propose a new way to image and move the drug precisely,” Xuejun Qian of the University of Southern California in Los Angeles, who led the latest research, said.

His team used a new form of “ultrafast” ultrasound imaging. It was capable of accurately tracking the progress of a cluster of “microbubbles” — tiny gas-filled bubbles that previous studies have identified as a means of transporting drugs through the vascular system — inside a mock blood vessel.

As the bubbles were being tracked the scientists were able to use a focused ultrasound transducer, a device that converts electrical energy into sound energy, to manoeuvre them. Known as “acoustic tweezers”, this type of system uses the mechanical energy of sound waves to manipulate tiny objects without making physical contact.

The scientists were also able to turn up the acoustic power to burst the bubbles, which would allow the drugs contained within them to be released only at a target site. Similar techniques have been used before but without the microbubbles being tracked using ultrasound imaging.

The experiments used a slender silicone tube to represent a blood vessel and tissue from a pig was used to play the part of a human body. In an early round of testing the microbubbles could be manoeuvred when they were up to a centimetre deep inside the tissue. The work was described in a study published yesterday in the journal Applied Physics Letters.

Previous trials, which used a less sophisticated microbubble system, had suggested that only about 1 per cent of an injected dose of chemotherapeutic drugs had reached the tumour.

The gas-filled microbubbles typically have a diameter of 0.5 to 10 micrometers. By comparison, a human hair is about 75 micrometers across.

Separate studies have suggested that it may be possible to use the acoustic tweezers without damaging living tissues. One trial found that red blood cells placed in an acoustic-tweezer device for up to 30 minutes showed no obvious ill-effects. The same was true of zebrafish embryos. Acoustic tweezers have also been used to manipulate nematode worms, apparently without harming them.

In part the technique is modelled on the development of so-called optical tweezers, which were invented in the 1980s. They have been used to trap viruses, bacteria and cells using beams of light.

However, traditional optical tweezers require complex optics and high-powered lasers, and are potentially damaging to biological material.