Artificial animalcules: in the microscopic realm, machines learn to swim.

Some 300 years ago, microscope inventor Antony van Leeuwenhoek stunned the world when he became the first to observe "animalcules" that were "very prettily a-moving" in human saliva and other excretions. Now, a human-rigged device has joined the menagerie. To a red blood cell, scientists in France have attached a wavy tail that responds to magnetic fields. When changes in those fields wiggle the tail, the -red blood cell swims.

Experiments with that device have given researchers insights into the physics that tiny swimming creatures have to master. Along with other micromachines making their way from the drawing board to the real world, such devices may someday prove useful in disease research or industry.

A tinge of science fiction, as well as hype, colors the endeavor. Notions of microscopic underwater craft trigger flashbacks to the 1966 movie Fantastic Voyage, in which a literally downsized medical team journeys aboard a tiny submarine inside a stricken diplomat's body to save his life. More recently, boosters of nanotechnology have repeatedly promised minuscule rovers capable of navigating human bloodstreams and dispensing medical treatments or reporting on local conditions.

The vision of medical microbots is not all fantasy, say researchers of scaled-down swimming gadgets. However, the task of devising these craft is challenging work, beset by complications that go far beyond the inherent difficulty of fabricating tiny gizmos.

Water--or any other surrounding liquid--affects micrometer-size objects in ways that are strikingly different from how it influences large-scale objects such as people, fish, or submarines. Researchers inventing propulsion mechanisms to exploit those unfamiliar circumstances find their own experiences in water to be of little help.

"Our intuition [about swimming] is based on the way objects our size move," notes Joseph E. Avron of the Technion-Israel Institute of Technology in Haifa. That intuition is "very bad for [understanding] small creatures."

"You have to ditch your previous concepts of how things swim," agrees mechanical engineer Anette E. Hosoi of the Massachusetts Institute of Technology (MIT).

LIFE'S A DRAG The underwater world of bacteria and swimming microcontraptions is so different from our world that it might as well be on another planet. Although the laws of physics remain the same for swimmers big and small, being as tiny as a bacterium makes them seem dramatically changed.

Why are microscale conditions so strange? Consider first the frictionlike force known as drag. Arising from contact between a fluid and a swimmer's surface, drag opposes motion through the fluid. The more viscous--or resistant to flow--a fluid is, the more drag it exerts.

Another characteristic, called inertia, resists changes in velocity. Inertia increases in proportion to the mass of a moving object.

A bacterium, say an Escherichia coli, has roughly a million times more surface area in proportion to its volume than does a person. So the effects of drag, compared with those of inertia, are much greater on an E. coli than on a person.

At the macroscopic scale, where inertia is large and drag is small, things in motion tend to stay in motion. In a pool, a person thrusts a hand or foot so that it launches water backward and pushes the swimmer forward in accordance with Newton's laws. Inertia then prolongs the swimmer's glide, although drag eventually slows it.

Under the topsy-turvy conditions of the microscale, however, swimmers can't launch liquid away from themselves because they can't overcome the drag of the water. And without much inertia, they don't glide. Swimming on the microscale is less like doing laps in the local swimming pool than it is like taking a dip in the asphalt goo of the La Brea tar pits on a warm day.

Whereas a macroscale propeller takes a mass of water and throws it backward, Avron says, the helical appendage, or flagellum, that propels an E. coli "is more like a corkscrew moving through cork:' Microscale swimmers scramble against the liquid or squirm through it in some manner that takes advantage of the fluid's viscosity.

WIGGLE ROOM Although scientists have known how viscosity, drag, and inertia act on microscale objects for decades, no one had found a way to exploit that knowledge to make an artificial swimmer of micrometer-scale proportions--until last year.

A group at the Ecole Superieure de Physique et de Chimie Industrielle in Paris was devising a way to straighten out loops in long, stringy biomolecules, such as RNA and DNA, to be used on microchips that detect gene activity. Remi Dreyfus first created filaments composed of microscopic magnetic beads joined by bundled DNA strands. Then, he used magnetic fields to make the beads pull apart, exerting tension on the DNA.

When Dreyfus watched videos taken with a camera-equipped microscope, he made a startling observation. "I could see that some filaments were swimming," he recalls. "It was really a surprise."

Dreyfus and his colleagues, including Howard A. Stone of Harvard University, soon found that the combination of steady and varying magnetic fields used to manipulate the beads was creating waves along the filaments that made a few of those chains swim around. The swimming chains had defects that made them asymmetrical, the team discovered.

To deliberately create asymmetry, the researchers attached one end of a chain to a red blood cell, which was an appropriate size and easy to affix.

By manipulating magnetic fields, scientists might direct their souped-up cell to a particular location. In this way, the team demonstrated that a swimming microdevice might do something useful, Dreyfus says. Instead of a red blood cell, the chain might deliver a vesicle filled with drug molecules or some other useful load.

Dreyfus and his colleagues "succeeded in attaching a mechanical engine to a biological creature. This was a wonderful piece of work," comments Avron.

To transform this first microswimmer into a device that carries out a specific task in the bloodstream would require many improvements, notes Jerome Bibette of the French group. To avoid having to remotely apply changing magnetic fields, researchers might need to endow the device with its own on-board motor and fuel supply and some amount of intelligence to navigate and report on its location. So far, the team has not secured funding to support such development.

Still, the device is more than just a toy. In the report in the Oct. 6, 2005 Nature in which the researchers unveiled the chain-driven red-blood cell, they also reported using it to confirm theoretical predictions correlating viscosity, tail elasticity, and other factors to speeds of spermatozoa in a saline solution.

Bibette says that the wavy filaments also look promising for potential use in disease research. As simple strands unattached to red blood cells, they might model other common biological machines, hairlike cilia. These structures are prevalent in microorganisms as a means of propulsion. The human body uses them, for instance, to clear mucus from airways. Malfunctioning cilia can lead to serious lung and kidney problems.

Bibette says that the French team plans to measure cilia-driven fluid flow while altering cilia properties, such as elasticity. Such studies could shed further light on microswimming, since moving fluid with cilia or moving bacteria that bear cilia are analogous processes, he notes.

SIMPLE STROKES While the first microswimming machine resembles one of nature's designs for a tiny swimmer, many other swimmers now on drawing boards stray far from what's known from biology. Physicists have dreamed up Tinkertoy-like designs as they have vied to meet the challenge in the simplest way.

In an off-cited 1970s lecture on microscale swimmers, Nobel prize-winning physicist Edward M. Purcell proposed a "two-hinged swimmer" as the simplest such gadget. The device would have three panels connected in series by two hinges. The outer two panels would move relative to the middle panel to propel the device forward.

Purcell suggested a series of movements of the microscale device's arms that would enable it to wiggle along a straight line in a specified direction. However, he left the details of why it would go that direction as "an exercise for the student."

In a recent investigation at MIT, Hosoi and Brian Chan tested Purcell's claims experimentally. They built a scaled-up model of the two-hinge apparatus, powered its arms with a windup spring, and immersed it in thick silicone oil to mimic the viscous conditions of the microworld. As can be seen in videos on the researchers' Web site (web.mit.edu/chosetec/www/robo/3link/), the model swims straight and in the direction Purcell claimed.

However, other researchers, including Harvard's Stone, have tackled Purcell's exercise with a theoretical analysis and found that the direction isn't as straightforward as Purcell imagined or as the mechanical testing indicates. In a 22-page report in 2003, the scientists concluded that although Purcell's gizmo should go straight, its direction depends on the size of the strokes made by its arms, a factor that Purcell didn't investigate.

Another Tinkertoy-style device proposed in 2004 consists of three balls connected in a line by arms that telescope in and out. The three-ball gizmo would move by a series of transformations in which each arm elongated or contracted, changing the spacing between the balls and propelling the device forward, reported Iranian physicists Ramin Golestanian of the Institute for Advanced Studies in Basic Sciences in Zanjan and Ali Najafi, now at Zanjan University.

Microswimmer designers have examined how quickly and efficiently the devices might move. For instance, Stone and his colleagues considered efficiency when they evaluated Purcell's two-hinge swimmer. Their calculations showed that the venerable device would be only a tenth as efficient as common microscale biological-propulsion structures, such as an undulating tail and a rotating helical flagellum.

Yet nature's solutions are not automatically the best. Indeed, there may be good reason to avoid mimicking biology, Avron suggests. "The history of flight was held back many years because at the beginning, everyone wanted to emulate nature and flap wings," he notes.

Avron and his Technion colleagues broke with natural design with a hypothetical construct that resembles two balloons connected by a thin, stretchy tube. The device propels itself in a series of choreographed steps in which each balloon is alternatively inflated and deflated as the tube elongates and retracts.

This device can theoretically outperform spermlike swimmers with beating tails, the inventors report in the November 2005 online New Journal of Physics. Given the reputation of sperm cells for speed, "it's like a turtle beating a hare" Avron says.

Studying the two-balloon device might yield some insights into biology because its movements vaguely resemble contortions that microbes known as euglena use to propel themselves, he adds.

A theoretical device propelled by couple of balloons is a long way from the miniaturized but complex technology that amazed viewers of Fantastic Voyage. Researchers have to find answers to many questions before even the simplest devices make their debuts.

How quickly and efficiently does the gadget move? How readily might it be built with current technology? Has nature already invented something better?

With each answer, researchers move closer to creating a new breed of animalcules to swim the microrealm.

TAIL GAIT--In a series of microscope images of a tiny, artificial swimmer (a to t), the pivoting of a magnetic field's orientation (White arrow) causes undulations Of the swimmer's tail. The wiggling tail propels an attached red blood cell gradually to the right. The microswimmer travels at a leisurely speed of up to one red blood cell diameter per second.

NEW BALL GAME--A hypothetical microswimmer composed of three rigid balls connected by telescoping rods (left) could locomote to the right by executing the shown cycle of rod extensions and retractions, theorists claim. TO also head to the right, another proposed contraption--two inflatable balloons joined by a flexible tube (right) cycles through its own series of swelling, shrinking, and tube-length changing.