New Device Better Diagnoses Blood Clotting Disorders

A new microfluidic device is able to detect how endothelial cells contribute to hemostasis.

When inflammation or dysfunction of the endothelium occurs, it may result in aberrant blood coagulation inside the vessels, and lead to life-threatening blockages or hemorrhage.

Previously, the interface between endothelial cells and circulating blood has not been accurately replicated in a practical diagnostic device, because of the challenges with incorporating living endothelial cells into a testing tool.

In a study published in Biomedical Microdevices, researchers discovered that endothelial cells do not need to be living in order to confer their effects on blood coagulation.

“Abnormal blood coagulation and platelet activation are major medical problems and the ways we study them now are overly simplified,” said Donald Ingber, MD, PhD. “Clinicians currently do not have tools to monitor hemostasis that take into account physiologically-important interactions between endothelial cells and flowing blood.”

Researchers microengineered tiny hollow channels that are lined by chemically fixed human endothelial cells that more closely mimic cellular and vascular flow conditions inside the body in order to monitor blood clot formation and diagnose effectiveness of anti-platelet therapy.

“It’s a bioinspired device that contains the endothelial function of a diseased patient without having actually living cells, and this greatly increases the robustness of the device,” said first study author Abhishek Jain, PhD.

The study authors noted that the blood coagulation diagnostics could be used to study the effects of endothelial inflammation on the formation of blood clots, information that is important for patients with atherosclerosis.

“This is one of the first examples of a how microfluidic cell culture system could have added value in clinical diagnostics,” said study co-author Andries van der Meer, PhD. “Using chemically fixed tissue that is no longer alive offers a clear, low-risk path toward further testing and product development.”

In prior studies, the research team was able to recreate the physicality and blood flow of vasculature within microfluidic channels. This allowed them to predict the exact times that blood might clot, with potential applications in real-time monitoring of patients given intravenous anticoagulants in order to prevent complications, such as vascular occlusion and stroke.

However, with the newest device the functionality of the vascular endothelium is embedded within a diagnostic tool that may be manufactured and shipped for clinical use — something that was never considered possible before.

“Our efforts to mimic the vascular system in a meaningful way within a microfluidic device has led to 2 avenues of technology development, which could potentially be combined in the future to develop portable tools suited for diagnosing and even discovering what disease states lead to blood clotting,” Ingber said. “Together they represent a new suite of physiologically-relevant microdevices that incorporate critical mechanical cues, and which could have near-term impact on our understanding and prevention of dysfunction hemostasis.”