Technology that shrinks laboratory procedures to the size of microchips is beginning to find applications in biomedical research, from counting HIV-infected cells to filtering harmful fats from the blood.

Diminutive device: Tiny channels on this chip can filter dangerous fats from the blood. Credit: Thomas Laurell

By borrowing techniques used to make microelectronics, chemists and engineers have spent several years building prototype 'labs on a chip.' The devices, carved from materials such as silicon, carry out bench experiments in miniature mixing chambers as small as a single cell.

Once considered cute curiosities, the gadgets are now being adopted by medical researchers and clinicians. They can process a tiny sample through multiple steps without human intervention, saving costly reagents, time and labor. “Now people are moving into true biology,” says Thomas Laurell, who studies nanotechnology at Lund University in Sweden.

One team, involving researchers at the University of Texas in Austin and Massachusetts General Hospital in Boston, has devised a small appliance for counting the disease-fighting CD4+ cells that are destroyed by HIV. Such counts are vital to gauge when a patient should begin antiretroviral treatment, and are currently carried out using a cumbersome flow cytometer costing at least $60,000 and confined to medical clinics.

The new device processes a single drop of blood on a tiny single-use chip. Once the blood is added to the chip, it flows through a series of reaction chambers where a fluorescent label recognizes and attaches to proteins on the surface of CD4+ cells. The chip sits in a machine about half the size of a toaster, which tallies up the labeled cells.

The portable device can be used in remote locations and will sell for about $1,500 when it becomes available later this year, says Rick Hawkins, chairman and CEO of the company marketing the technology, called LabNow, in Austin, Texas. The team members say they are adapting the technology to take other measurements such as the viral load in blood.

Laurell's group has developed a chip the size of a postage stamp for combating a perennial problem encountered during surgery using a heart-lung machine. Sometimes, lipids leak into the blood from fat tissue damaged during the operation and cause tiny clots to form in the blood vessels of the brain. Methods currently used to filter out these lipids are not completely effective and can damage blood cells.

In the new system, blood flowing through a channel is subjected to sound waves that exert pressure on the blood cells and lipid particles. Because the two components are different densities and respond differently to the pressure, they move in different directions and into separate tubes (Lab Chip 5, 20–22; 2005). Laurell's group is scaling up the technology to filter liters of blood by using multiple chips in parallel.

Though many of these devices have yet to find a commercial market, the technology is coming into its own in basic research. Miniature machines for culturing cells, for example, are thought to mimic the subtle microenvironment around cells better than conventional culture dishes. Researchers have grown single neurons on a chip and measured their electrical activity (Lab Chip 5, 97–101; 2005) and measured insulin secretion from pancreatic cells (Lab Chip 5, 56–63; 2005).

But despite their progress, those in the field say the technology is still some way from being widely accepted by researchers and doctors, who are often reluctant to give up tried and tested techniques. “Not only do you have to show that you can do it better and cheaper,” says biomedical engineer David Beebe at the University of Wisconsin, Madison, “but you have to get doctors to change the way they do medicine.”