Chip Device Simulates Blood Vessels in Clotting

Blood vessel simulation chip (Wyss Institute, Harvard University)

10 August 2016. Researchers at a Harvard University bioengineering center developed a plastic chip that simulates critical interactions between tissue lining blood vessels and platelets that affect the flow of blood. The team from Harvard’s Wyss Institute for Biologically Inspired Engineering describe the device in a recent (27 July) issue of the journal Biomedical Microdevices.

Wyss Institute director and senior author Donald Ingber and colleagues are seeking a platform to simulate the process in which blood coagulates or clots in response to blood vessel injuries, preventing excessive bleeding. Clots can also cause blockages in blood flow leading, for example, to strokes. A key part of that clotting process is the interaction between tissue lining the inside of blood vessels known as endothelium and platelet cells that form into clots.

A device that simulates this process, called hemostasis, would promote a better understanding of the way clots develop under various conditions, help develop diagnostics for coagulation disorders, and screen drugs that enhance or discourage clotting. Up to now, however, the inability of endothelium cells to survive outside the body made it difficult to create this device. The Wyss Institute team led by postdoctoral researcher and first author Abhishek Jain were able to overcome this obstacle in their new device.

The device is a microfluidic or lab-on-a-chip about the same size as a standard 75 by 25 millimeter microscope slide, with microscale channels etched into common PDMS polymer plastic. The channels are lined with endothelium tissue from umbilical cord veins, activated with growth factors, then incubated in a formaldehyde solution to chemically preserve or fix the state of the endothelium cells. This fixing step preserves the functioning of endothelium cells, while making them able to survive outside the body.

The Wyss Institute team demonstrated the chip with small samples, 0.5 milliliters, of whole blood from individuals taking medications that inhibit platelet accumulations, including aspirin and clopidogrel, marketed as Plavix by Bristol-Myers Squibb. With the device, researchers were able to demonstrate platelet functioning and clot formation, indicating its value for diagnostics and point-of-care applications.

The researchers say the chip can also be used to diagnose inflammation of endothelial tissue in blood clots, related to atherosclerosis, the build-up of plaque leading to hardening and narrowing of blood vessels. “It’s a bioinspired device that contains the endothelial function of a diseased patient without having actual living cells, and this greatly increases the robustness of the device,” says Jain in a Wyss Institute statement.

A U.S. patent application is pending for the technology. Ingber and co-author Geraldine Hamilton are founders of Emulate Inc., a two year-old company in Boston developing chip devices simulating human organs. As reported in Science & Enterprise, Emulate Inc. attracted $28 million in new venture financing in March 2016.

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