ARLINGTON , Va. , Aug. 2, 2005 — A tiny chip that mimics the circulatory system—right down to the rhythm of a human heartbeat—could be a valuable tool for understanding the causes of cardiovascular disease and for developing drug therapies.

In the July issue of the journal Analytical Chemistry, researchers at the University of Michigan (UM) describe the system of tiny valves and channels on the chip that mimic blood flow in the body. This allows scientists to study the fluid mechanical effects of blood flow (called shear stress) on endothelial cells, which line the inner walls of blood vessels and play a critical role in heart disease.

Changes in the flow rate and rhythm of blood can cause changes in endothelial cells. Medical researchers want to know how these changes can lead to diseases, such as hardening of the arteries or thrombosis. Answering such questions will provide big clues to developing therapies.

The chip's central feature is a pin system that was originally designed for a device that helps the visually impaired read e-mail, says Shuichi Takayama, Ph.D., a UM biomedical engineering professor and corresponding author on the paper. Originally, the pins moved up and down beneath a reader's fingertips to represent certain Braille letters, thus translating what appears on the computer screen.

In the U-M invention, the pins move up and down to plunge fluid through a system of tiny channels drilled into the chip. The pins function as the heart of the system and the channels as the vasculature. A computer program acts as the brain of the system to control pin movement, or the heart beat, and regulates fluid flow patterns, or the pulse, through the vasculature.

The chip with the endothelial cell-lined vasculature is assembled in three layers and sits on top of the pin system. The researchers reported that the microfluidic blood flow caused endothelial cells on the chip to significantly align and elongate in the direction of the flow and in relation to the levels of shear stress.

Studying endothelial cells in a Petri dish is often ineffective because the test environment is static, like bath water, says Takayama. The cells are not acting as they would in the body where they are exposed to flow, like in a river, he says. But with the U-M system, scientists can adjust the flow through the channels on the chip so that the endothelial cells think they are inside an artery or vein, or maybe even inside the blood vessels of a couch potato or a regular exerciser.

Existing model systems that attempt to closely mimic true physiological flow conditions of blood in the body cannot perform multiple experiments, are not easily portable, consume large amounts of reagents, and can become contaminated easily, the researchers said.

The U-M team's chip differs from others because the intricate system of pumps and channels lets researchers sustain high levels of shear stress on the cells for hours or days, with various patterns of flow similar to the way in which endothelial cells in the body are exposed to changing shear stress levels caused when blood flows past the cell. The microfluidic valving and pumping system lets researchers perform different tests simultaneously in multiple channels on the same chip.

Takayama received a Whitaker Research Grant in 2001 titled Multi-Dimensional Cell Profiling Using an Artificial Endothelium.

Shuichi Takayama, University of Michigan
Mark Bowman, The Whitaker Foundation