November 23, 2012 7:20 pm

Levitation lifts drug hopes

Technology invented by Nasa can help lower drug doses by changing the physical structure at which they solidify
Chris Benmore uses 'acoustic levitation' to simulate weightlessness of droplets©Wes Agresta

Droplets are suspended in mid-air as Chris Benmore uses 'acoustic levitation' to simulate weightlessness

Chris Benmore looks like a magician as he floats balls and droplets in mid-air – and then moves them around by twiddling the dial on his “levitator” at Argonne National Laboratory, near Chicago. Benmore is indeed an accomplished showman but he is working in the cause of science and, in particular, the quest to make better medicines.

If you keep a liquid levitated as it cools and solidifies, its physical structure may end up quite different from the same material cooled in an ordinary container – because a drop suspended in mid-air has no contact with a surface that can trigger crystallisation. Instead of solidifying in its usual crystal structure, the compound is more likely to freeze as an “amorphous” or glassy material. And that can make a big difference if it is a drug.

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Drugs dissolve in water more readily if they are in amorphous rather than crystalline form and they work more efficiently in the patient, which means that much lower doses can be given. “You can achieve a tenfold to hundredfold dosage reduction,” says Stephen Byrn, professor of medicinal chemistry at Purdue University, who is working with the Argonne physicists to apply the technology to pharmaceutical development.

The technology is based on acoustic levitation, invented by Nasa to simulate weightlessness. Small speakers generate intense sound waves at about 21 kilohertz, just above the audible frequency range for adults (I could just hear a high-pitched whine when the equipment operated at high volume). When the top and bottom speakers are aligned, their interference creates a series of “standing waves”. These contain stationary “nodes”, invisible pockets in which the acoustic pressure is strong enough to counteract the downward force of gravity. By changing the frequency and power of the sound generators, Benmore can move levitated objects up and down the central column and even create secondary nodes to the side.

The apparatus operates at Argonne’s Advanced Photon Source, where the scientists use an X-ray beam to study the internal structure of materials. For this project they will discover how and why drugs remained amorphous or crystallised as they solidified in the levitator.

The researchers will screen new and existing drugs to see which insist on crystallising under even the best conditions – and which could be manufactured in amorphous form, perhaps by adding polymers that help to stave off crystallisation. “At the moment this is completely unpredictable from a drug’s molecular structure, so screening with the levitator will be very useful for pharmaceutical research,” Byrn says. He believes it could be particularly valuable for Aids drugs, which are especially prone to turn out as insoluble “brick dust”.

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Argonne past, present and future

Argonne, established in 1946, is one of a dozen national laboratories that the US government set up in the aftermath of the second world war. Its aim was to consolidate America’s position as the world’s leading power in science and engineering, particularly as applied to energy, weapons and national security.

These days the labs are under the wing of the Department of Energy but still command a generous share of the federal research budget. They are less secret than they used to be, though even the less security-conscious labs such as Argonne require non-US citizens to complete a formidable form well ahead of any visit.

Argonne, in the Illinois suburbs southwest of Chicago, employs 3,400 full-time staff with an operating budget of $750m a year. It covers a wide range of research, particularly in materials science, chemistry and physics.

Eric Isaacs, the lab director, says Argonne and its sister DoE institutions, play a distinctive role in delivering innovative research and technology. “The universities do great science and can spin out great companies but we are more mission-driven than them,” he says. “We approach the really big problems, such as making batteries and energy storage much more efficient, with a different imperative.”

The national labs are also carrying out work that used to be done by the great corporate laboratories such as Bell Labs, where Isaacs once worked. Companies have largely pulled out of research that does not have a relatively short-term application.

Another role for Argonne is to organise public-private partnerships to tackle big issues, says Isaacs: “We are good at acting as a trusted partner to pull together groups of competing companies and universities to work together on a common problem.”

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Delving into Picasso’s ‘house paint’ period

A powerful new tool is helping in the scientific analysis of art – ultra-intense X-ray beams generated by machines called synchrotrons, which can probe the internal structure of a vast range of materials from microbes to metals. Although European synchrotrons led the way in cultural studies, Argonne’s Advanced Photon Source has now come up with fascinating findings about Pablo Picasso’s paints.

Francesca Casadio, conservation scientist at the Art Institute of Chicago, collaborated with Argonne physicist Volker Rose to prove that Picasso used house paint, as well as traditional artists’ oil paints, at various points in his career. There was some documentary evidence that Picasso worked with a well known French brand of commercial paint, Ripolin, but art historians were not sure how extensively.

By travelling through France – and buying vintage paint on eBay – Casadio built up a database of Ripolin samples. She also obtained samples from several Picassos painted over more than three decades. When the samples were compared, there was no doubt that the pigment from the Picassos was Ripolin rather than artists’ oil paint.

In future pigment analysis by synchrotron radiation could become a useful tool for investigating old master paintings whose provenance or authenticity is in doubt, Casadio believes.

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Li-ion is king of the car battery jungle

Battery research, particularly for electric vehicles, has become one of Argonne’s biggest programmes over the past four years. “I have been working on batteries here for 12 years but the research really came to prominence after President Obama came to power,” says Argonne scientist Dan Abraham.

Argonne technology reached the market last year in the Chevy Volt from General Motors, the first plug-in hybrid electric car. Abraham says its lithium-ion (Li-ion) battery, using fundamentally the same reaction as the tiny cells that power mobile phones and laptops, performs better than any other car battery on the market.

Web of intrigue

A spider

A study at Argonne shows that spider silk’s unique combination of strength and elasticity is achieved through fibres of both crystalline and uncrystallised protein knitted together into strands.

The programme is moving ahead on a broad scientific front in collaboration with industry to pack more energy into a given size and weight of battery, reduce its charging time and, most importantly, extend driving range. Argonne researchers expect to increase the distance between recharges from about 160km today to 200km by improving existing Li-ion cells.

To give electric cars a range of 500km, similar to a petrol or diesel car between refuelling, will need a fundamental change in technology – and Argonne has taken on the challenge, pinning its hopes on lithium-air batteries which could theoretically pack in five to 10 times more energy than Li-ion.

“The physics tell us that we can do it,” says lab director Eric Isaacs, “but extensive collaboration across many disciplines and organisations over many years will be needed to pull it off.”

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