By Laura Bailey

In May 2000, the drinking water in the town of Walkerton, Ontario, started killing people. By the time Canadian environmental workers could analyze and identify the problem as E. coli and get it under control, seven people died and 2000 became seriously ill. The Canadian government spent an estimated $155 million on the incident. Real estate values in Walkerton collapsed. And the town spent $651,000 to supply bottled water to its citizens and to disinfect or replace water-purification equipment.

If authorities had been able to analyze Walkerton's water quickly, easily and accurately, they might have been able to eliminate the E. coli long before the problem turned into a catastrophe. But this would've required a device -- preferably handheld -- that environmental watchdogs could have carried to various locations to analyze the water immediately and with precision. And for a rural area with limited resources, it wouldÕve been helpful if the device were relatively inexpensive, which means the process for making it needed to be fast and efficient.

This portable device and the process for making it now exist. It's a small but well-equipped "laboratory on a chip" that College of Engineering researchers created by using an ultrafast laser to produce features as small as 50 nanometers -- a scale that's almost unimaginable. (A pinhead is one million nanometers in diameter.)

Machining at an Infinitesimal Scale

Top view of three microfluidic channels machined in an elastomer atop glass. A U-shaped nanochannel (vertical line) drilled in the glass passes under the center channel to connect the two outer channels.

Until recently, there's been no easy way to machine a wide variety of materials to make parts and build devices at the nanometer scale. But in this new era of "nanomachining," an ultrafast laser burst lasting just quadrillionths of a second ablates (cuts away or evaporates) the toughest materials, such as silicon, glass, quartz and sapphire. In addition to its extraordinary power, this same system, developed by Michigan Engineering's Center for Ultrafast Optical Science (CUOS), also is sufficiently precise to cut the membrane of a human cell without causing any collateral damage.

Alan Hunt, associate professor, Biomedical Engineering, said that "even techniques with capabilities close to the ultrafast laser are able to machine in only one plane -- they don't allow machining below the surface or within a material." (See sidebar: Other Nanomachining Methods.)

Machining on one plane is very limiting. As the number of channels and other configurations increases, the plane must increase in size. The complexity of t he machining is an issue, too, because channels carved at right angles to each other eventually cross; in a microfludic device, the fluids traveling along these crossed micro-channels would mix -- a

Other Nanomachining Methods Nanomachining with the ultrafast laser has proved to be the most effective, efficient and precise method to ablate materials, be they inorganic or organic. However, there are other methods, but they're limited to machining in only two dimensions. Surface modification with an atomic force microscope (AFM) is one of the surface processing techniques in the nanometer scale. This technique is a complicated mechanical processing of scratching on a nanometer-scale. EUV lithography is a nanomachining method in which X-rays generate "excitons" in materials and a resultant absorption of ultraviolet light (UV) which ablates materials in two dimensions. Focused Ion Beam (FIB) nanomachining uses a probe (a metal-coated tungsten needle) to emit a column of ions which are focused on a metal surface. The impinging ions release secondary ions from the surface of the metal, creating a "sputter erosion" and removal of material. Electron Beams can be focused onto targets in a vacuum; if an appropriate material is used, energetic electrons remove material at the surface.

circumstance that would undermine the function of the device. "However," Hunt said, "the unique physics of the ultrafast laser allows machining in three dimensions. That is, we can do machining on a number of planes within a solid. If we have three channels on a plane, we can link the outer two without cutting into the center one, we can go down, over and up -- we can cut a U-shape. Not being constrained to one plane, the level of complexity that can be achieved is much greater."

Additional Uses of Ultrafast-Laser Nanomachining

Nanomachining with the ultrafast laser has yielded substantial results and has attracted the attention of researchers who are eager to see if its precision cutting can help them in their work.

Structural knockouts -- Hunt and U-M Medical School's Dr. Deborah Gumucio are using nanomachining to help them understand the inner workings of cells and tissues. By machining a single cell, Hunt can knock a tiny piece of the cell out of commission without killing the whole cell, a capability that enables Hunt and others to study precisely how the cell works. For example, Hunt is collaborating with Gumucio, who studies a protein called ASC, which many believe is a central regulator of the innate immune system and is thought to play an important role in various inflammatory diseases, such as familial Mediterranean fever. Under some conditions, ASC forms macromolecular structures called "specks"; the formation of specks seems to presage the death of the cell.

"If you wanted to design a drug to go treat this sort of inflammatory disease," Hunt said, "you need to know what the drug target should be. Suppose you see a structure in a cell and you believe it causes the cells to die. You go in with the laser and you destroy that thing and say, 'Does the cell live?' It's a conceptually very simple experiment. In a sense you're machining the cell."

In the future, using ultrafast-laser nanomachining to do structural knockouts might enable doctors to remove diseased tissue -- even a single deleterious gene -- at a sub-cellular level. This could have applications such as treating or preventing cancer.

Nanopores -- Michael Mayer, assistant professor, Biomedical Engineering, Chemical Engineering, uses this ultrafast-laser nanomachining technology to

Making this 50-nanometer pore -- a significant step in an ongoing effort to create pores 15 nanometers in diameter -- made it possible to detect a virus, one of many applications that will make these pores useful in making medical diagnoses and detecting biological warfare agents.

drill holes just 50 to 200 nanometers in diameter in a glassy surface. These "nanopores" enable researchers to detect nanoparticles, including viruses and large proteins. As a particle moves through a nanopore, the pore's electrical resistance increases. By detecting this impedance, researchers can count individual particles, an ability that might someday be useful in making medical diagnoses and detecting biological warfare agents.

Nanopores might also be useful in developing drugs. "Patch clamping" is a common technique used to develop drugs for the heart, brain and other tissue with electrically active cells. Right now, patch clamping requires a sophisticated user who can steer a glass pipette less than a micrometer wide into a cell to record electrical impulses -- a very delicate procedure. Nanopores have simplified this process: Scientists place the cells over the nanopores and, as electrical current passes through the pores, the cells' impedance yields data that can accelerate drug development and subsequently reduce costs.

MEMS construction -- Ultrafast-laser nanomachining has potential in the construction and repair of microelectromechanical systems (MEMS), such as sensors in airbags.

Photolithography -- Nanomachining could come in handy in building and repairing the masks and stamps used in photolithography to make electronic components such as computer chips. The efficiency of ultrafast-laser nanomachining will reduce development costs and the subsequent prices that consumers will pay.  -E

Laura Bailey is a science writer for the University of Michigan.