All Work And Some Play

Toys are not just for kids, but also researchers, as Scientific American points out in an article about how some of your fond playthings have become instrumental in labritory situations:

Advances in science and technology can launch from unassuming springboards. In 1609 Galileo tweaked a toylike spyglass, pointed it at the moon and Jupiter (not the neighbors), and astronomy took a quantum leap. About 150 years later, Benjamin Franklin reportedly used a kite to experiment with one of the earliest-known electrical capacitors. Continuing that tradition, these researchers prove toys inspire more than child's play.

Etch A Sketch
"The laboratory is basically a glorified playroom," says Jeremy Levy, physics professor at the University of Pittsburgh. "When we do experiments, it is a highly advanced form of play…we're exploring new things."

Levy's current explorations stem from his memories of a childhood drawing toy. While visiting Germany's University of Augsburg in 2006, he observed a tiny chip made of two insulating layers. The chip intrigued Levy because the area between the layers could switch properties—from insulating to conducting, and back again—when researchers applied voltage. "While they were showing me the data, I was thinking about Etch A Sketch," Levy says.

To draw lines, the toy's stylus scrapes aluminum powder from the underside of a glass screen. Levy wondered if an Etch A Sketch approach could build on the German researchers' findings to draw and erase nanowires?

Using an atomic force microscope and two layers of insulators (lanthanum aluminum oxide and strontium titanium oxide), Levy and his colleagues created a nanoscale transistor. Unlike the Etch A Sketch, their technique did not involve scraping. When the microscope's sharp tip applied a positive voltage to the material's surface, it drew conducting lines that exist in the space between the oxide layers. This allowed researchers to make wires two nanometers wide. (A nanometer is one billionth of a meter, or about 40 billionths of an inch.) Published in Science last year their work also overcomes a perennial Etch A Sketch frustration—one false move, and you must erase the whole darn thing. Not so with the nanoelectric Etch A Sketch, which can selectively erase the conducting lines it creates by applying negative voltage.

The transistor is about 1,000 times smaller in area than silicon-based transistors used in electronics today, Levy says. Someday, it could quench the semiconductor industry's thirst for ever-shrinking components. But not yet: "There's a big step between making one transistor and making hundreds of millions of them that all work."

Legos
Few kids would equate fun with "Directional Locking and the Role of Irreversible Interactions in Deterministic Hydrodynamics Separations in Microfluidic Devices"—a 2009 Physical Review Letters paper co-authored by Joelle Frechette and German Drazer, assistant professors in Johns Hopkins University's Department of Chemical and Biomolecular Engineering. But the main tool in that research happens to be a popular toy.

Because Legos are easy to reconfigure, they are an engrossing plaything for kids—and a pragmatic tool for the Johns Hopkins researchers. "It let us really do good science," Frechette says. She and Drazer studied a particular microfluidics technique used to separate mixtures of particles. Microfluidics involves the manipulation of fluids (sometimes in picoliters, or trillionths of a liter) through tiny channels. Often referred to as a "lab on a chip," microfluidics devices have a range of applications, including medical diagnostics and drug delivery. To test the underlying mechanisms, they built a large-scale structure that helps mimic the behavior of microscopic particles.

For the particle-separation experiments, the researchers covered a large Lego board with cylindrical Lego pegs and placed the board vertically in a fish tank filled with glycerol, a viscous liquid. They dropped various-size ball bearings into the tank and watched the balls' trajectories around the pegs. "It's a little like a pachinko machine," Frechette says, referring to a type of vertical pinball gaming machine found in Japan. Researchers rotated the board to see how different angles affected the results, and dropped hundreds of balls to obtain the statistics they needed.

About $50 worth of Legos were used for the study. Including the ball bearings and glycerol, Frechette estimates the entire setup cost less than $300. "I have students who spend that much on chemicals in one day," she says.

Shrinky Dink
When Michelle Khine first shared her idea for Shrinky Dink microfluidics, she worried some would deem it half-baked. "One of my former lab mates said, 'You do realize that people are going to love this and it's going to revolutionize everything—or they're going to laugh at you.'" In 2008 Lab on a Chip (a Royal Society of Chemistry journal) published Khine's work. It was one of the journal's top three most-accessed papers that year, and she received dozens of e-mails from labs worldwide expressing praise, not derision.

As a child Khine spent countless hours creating designs on Shrinky Dink plastic and watching them shrink in the oven. Years later she returned to her favorite toy out of necessity when, after joining a brand-new university, she lacked much-needed facilities for making microfluidics chips. The Shrinky Dink inspiration struck Khine one evening while spending time in her kitchen ("It's where I do most of my thinking," she says).

Khine knew that when Shrinky Dinks condense, any ink lines on the plastic become raised—and that's precisely what she sought in a microfluidics mold. She bought Shrinky Dink plastic designed for computer printer use, printed a pattern, and baked it for several minutes in her toaster oven. The results exceeded her expectations. Instead of just making molds, Khine ultimately developed a technique to make microfluidics chips directly from Shrinky Dink plastic. "It actually worked really well," Khine says, well enough to found a company based on that basic premise. To create products such as stem cell research devices and solar cells, Shrink Nanotechnologies has developed a new material that trumps the toy's abilities. Says Khine: "Shrinky Dinks shrink by 60 percent, but our new polymer shrinks 95 percent. And the properties shrink more consistently."

Balloon within a Balloon
One morning in 2002 Shiladitya Sengupta gazed out a train window and saw the solution to a vexing problem. He and other cancer treatment researchers wanted to transport chemotherapy drugs inside a tumor after blocking its blood supply. "It's almost like, how do you fill a bucket of water after the tap has been shut off?" says Sengupta, an assistant professor of medicine and health sciences and technology at Harvard Medical School in Boston.

His epiphany came after spotting a vendor who sold balloons inflated inside larger balloons. Sengupta realized the balloon-within-a-balloon structure could help him tackle the drug delivery challenge. He envisioned a bigger "balloon" that would burst and release drugs to shut off tumor blood vessels—then a smaller balloon would release chemotherapy drugs. "I think people were surprised by the simplicity of the idea," he says.

Sengupta and his colleagues parlayed that balloon breakthrough into a new strategy for cancer treatment: a nanocell. "We called it a nanocell because it looks like a nucleus and surrounding lipid structure, but it's significantly smaller than a cell," Sengupta says. Measuring less than 200 nanometers, the nanocell contains different drugs in each of its two layers. In 2005 Nature published details of this particular drug delivery. (Scientific American is part of Nature Publishing Group.)

Sengupta later co-founded Cerulean Pharma, Inc., which focuses on nanotechnology-based treatments. Although its current products are based on single drugs, the company does hold a license to develop dual-drug nanocells. Other scientists have adopted Sengupta's balloon-within-a-balloon idea. A research group at Boston's Massachusetts General Hospital, led by Tayyaba Hasan, has used nanocells and photodynamic therapy (light-activated chemicals) to target pancreatic cancer. They presented the results of their work with mice in November 2009 at the Molecular Targets and Cancer Therapeutics conference. It is too soon to predict when human trials will begin for their nanocell treatment, says Hasan. "'As soon as we can' is the short answer."