Obstacle course. On the left, a droplet moves toward the dashed box along the shortest path. On the right, the droplet goes astray at two locations but corrects its trajectory and ultimately finds the shortest path.

Istvan Lagzi, Bartosz Grzybowski, et al., JACS

Oil Drop Navigates Complex Maze

Lab rats, watch your back. Scientists have found a way to make simple droplets of oil navigate complex labyrinths with the same skill as laboratory rodents. The advance could help researchers devise better ways to solve other mazelike problems, from rooting out cancer in the body to mapping paths through traffic jams.

Physical chemist Bartosz Grzybowski of Northwestern University in Evanston, Illinois, and colleagues hit upon the droplets while trying to devise novel cancer therapies. Scientists have developed a variety of ways to get cancer drugs into the body--including nanoparticles and liposomes--but all face the same obstacle: It's hard to navigate the body's maze of vessels and tissues to seek out and destroy hidden cancers.

So Grzybowski's team made a number of silicon mazes roughly 6.5 square centimeters in size. To create the conditions for movement, the researchers filled the labyrinths with an alkaline solution of potassium hydroxide. The maze runners, placed at the entrance of the labyrinths, were millimeter-wide droplets of either mineral oil or the organic solvent dichloromethane, both loaded with a weak acid and red dye. The "prize," placed at the exit of each maze, was a lump of agarose gel soaked in hydrochloric acid. "We wanted to give [the droplets] a bit of a challenge and see if they could do more than just go in a straight line," Grzybowski says.

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Pulled along. Watch a droplet navigate a silicon maze.
Istvan Lagzi, Bartosz Grzybowski, et al., JACS

Over the course of a minute or so, each droplet found its way to the end of the maze. The reason they move in the right direction has to do with basic chemistry. Acid from the highly acidic gel slowly leaks into the potassium hydroxide solution that fills the maze, creating a gradient: Solution near the exit becomes more acidic, whereas solution near the entrance stays more basic. This basic solution interacts with the acidic droplet, causing the part of the droplet facing the exit to become more acidic than the part of the droplet facing away from the exit. The disparity increases the surface tension of the side of the droplet that faces the exit--and it's this difference in surface tension between the two sides of the droplet that propels it toward the exit of the maze.

The mineral oil droplets always found the shortest possible paths through the maze. "We can call them chemo-rats," Grzybowski says. The droplets made from dichloromethane traveled at faster speeds--perhaps because acid was released onto their surfaces at a higher rate--and thus sometimes veered onto the wrong paths, but they always reverted rapidly to the best ways out, the team reports online 11 January in the Journal of the American Chemical Society.

So how does all of this relate to cancer therapy? Grzybowski notes that cancers are more acidic than the rest of the body, so--like the maze droplets--one could potentially design drug vehicles to follow the acid-base gradient toward the cancer cells.

The work could even have implications beyond medicine. Grzybowski says that in some cases, when his team simultaneously introduced two droplets into mazes, they almost never got in each other's way on their way out. "You can imagine designing systems that might be of some interest for traffic people investigating urban navigation," he notes. Chemist John Pojman of Louisiana State University in Baton Rouge adds that such roving droplets "might be useful as a pumping mechanism for microfluidics, converting chemical energy to mechanical motion in small devices," such as the microfluidic labs-on-a-chip many researchers are developing as diagnostic machines.

Computers and mathematics could also benefit. Maze navigation can fall into a class of problems known as NP-complete, "which computers have a surprisingly hard time solving, as the effort to solve them goes up exponentially with the scale of the problem," says chemist Irv Epstein of Brandeis University in Waltham, Massachusetts. "The kind of approach shown here with these mazes might be a very efficient approach to address this problem." One would then want more complex variations, he notes. "Perhaps more complex kinds of gradients, mazes with multiple exits, and setting this up not just in two dimensions but three."