ARLINGTON, Va., Nov. 4, 2002 --- Biomedical engineers at Harvard Medical School have developed a tiny tool to study how chemicals attract cells, a key step in immunity, healing, and fighting the spread of cancer.

In the August issue of Nature Biotechnology, researchers describe a microfabricated device and new technique to study the cell-attracting process of chemotaxis much more precisely than ever before.

"We can use these kinds of devices to see how cells move in response to complex chemical cues," said Mehmet Toner, Ph.D., the lead researcher and a professor at the Center for Engineering in Medicine and Surgical Services at Massachusetts General Hospital and Harvard Medical School.

Nobody has tapped into this area yet, Toner said. A major application could be in developmental biology to understand how different cells work together to form organs.

Chemotaxis occurs when changes in the concentration of certain chemicals or molecules attract or, in some cases, repel cells and other microorganisms. This process plays an important role in helping antibodies find and kill harmful organisms, in helping the cells of an embryo develop, and in keeping cancer cells from spreading.

Over the past 40 years, experiments in chemotaxis basically placed cells on one end of a microscope slide or lab dish and the attracting molecules, or chemoattractant, on the other side, and then watched the cells to see how many and how fast they moved. Such experiments could determine a threshold level of "on" or "off." But a different approach is needed to find out what happens between these two extremes.

To that end, the research team created a chip containing several microscopic fluid channels significantly less wide and deep than the imprint of a human hair. All channels converge into one shallow channel, where different concentrations of chemoattractant from the different channels flow side by side without mixing.

These "streams within a stream" flow over cells scattered on the bottom of the channel. The researchers can observe how the cells move and react to a high concentration along one "bank" of the stream that gradually tapers off to a very dilute concentration on the opposite bank.

The researchers used the device to measure the response of neutrophils, which guard the body against infection, to varying levels of interleukin-8 (Il-8), a protein marker for infection, injury and inflammation.

Many of the neutrophils migrated toward gradually higher concentrations of Il-8 up to the point of highest concentration, but usually not farther. However, when neutrophils encountered a sharp peak in chemical attractant in the center of the channel's stream, some cells clustered in the middle of the channel while other cells overshot the peak concentration and kept moving away from it.

This difference in response to gentle versus sharp transitions indicates that there is a complex sensing mechanism for cellular movement that is not well understood, Toner said.

The Whitaker Foundation awarded Toner a three-year research grant in 1993. Currently, he is finishing work on a three-year Special Opportunity Award from the foundation to develop a biomedical engineering research and education program through the Harvard Medical School.

Mark Bowman, Whitaker Foundation