" he said. Microfluidic technology can address this issue through its ability to control complex reactions at critical times and locations.

In previous work, the Ismagilov group designed a simple laboratory model to simulate blood clotting. In this model, Ph.D. student Runyon and his associates devised three modules that correspond to the three major stages of clotting: production of chemicals that activate clotting, the inhibition of these activators, and formation of the solid clot.

In this model, the scientists used only one chemical reaction in each module instead of the 20-to-30 biochemical reactions that the modules represent. Surprisingly, this simple model adequately reproduced many features of blood clotting.

"There’s a long history in chemistry of using simple models to understand more complex behavior," Kastrup said. "Instead of looking at hundreds of equations for blood clotting, we reduced it down to three main equations. From these equations we were able to describe a lot of the dynamics of clotting."

The ability of microfluidics to mimic the flow and geometry of human blood vessels also proved critical.

"We had to use microfluidics to do all of this because that's how we controlled where everything is," Ismagilov said of Runyon's previous work. "It turned out that we got appropriate behavior only if we used geometry similar to those observed in our vascular system. If we changed the geometry to something that didn't look like a biological system, the chemical system couldn’t function. So geometry and flow were very important."

In the latest advance, Kastrup used Runyon's model to see if he could predict when clotting would occur in human blood. The team predicted and verified that clotting occurs only at locations of vascular damage larger than a critical size. "Surprisingly, this simple model made correct, quantitative predictions about blood clotting," Kastrup said.


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