A ‘laboratory’ the size of a postage stamp could be the next big thing in the search for safer anticlotting drugs to prevent heart attacks and strokes.

The effectiveness of current anticlotting medications can be limited due to the risk of complications, driving a need for alternatives that can both prevent the formation of blood clots and reduce the risk of excessive and life-threatening bleeding.

The new biocompatible ‘lab-on-a-chip’ has been developed by a team of biochemists and engineers at the Royal Melbourne Institute of Technology (RMIT) and the hematology microplatforms group at the Australian Center for Blood Diseases (ACBD).1 The technology, which shrinks a medical pathology laboratory onto a small chip, features automated processes that can achieve in a few minutes what could take days in a full-sized lab. Its developers say the technology could help accelerate the discovery and development of new anticlotting therapies.

The new device is designed specifically to work with the complex and sensitive biology of blood, featuring a unique system of micropumps and analysis tools for testing the effect of chemical compounds on how the blood clots. The device is based on microfluidic chip technology developed at RMIT’s micro nano research facility (MNRF) and within the vascular biology laboratory at Monash University.

Lead investigator Warwick Nesbitt, PhD, senior research fellow at RMIT and group leader at ACBD, is working with collaborators at ACBD to use the pioneering device to better understand clotting mechanisms and develop new anticlotting drugs. Nesbitt says very few microdevices developed to date are suitable for clinical or research use because most have not been driven by insight into how blood actually behaves.

“Blood is extremely sensitive to artificial surfaces and clots very easily, so blood-handling technologies must be equally sensitive,” says Nesbitt. “We’ve combined a deep understanding of the biology of blood with precision microfabrication engineering and design to deliver a device that can work with whole blood and produce reliable results. We hope this powerful new tool will give researchers an edge in delivering better and safer anticlotting treatments to improve the health and well-being of millions around the world.”

The microlab can screen hundreds of drug compounds in just a few hours, revealing their effect on blood and quickly identifying those that have the greatest potential for clinical use. The microfluidic chip contains an array of miniature channels, valves, processors, and pumps that can precisely and flexibly manipulate fluids. The chips combine speed, portability, and capacity, handling vast quantities of tiny processing elements. They are also scalable and cheap to produce.

The microfluidic technology was combined with a sensitive assay for testing how platelets respond to different chemical combinations. In a proof-of-concept application, the microlab was used to investigate how dosing blood with select small molecule inhibitors affects platelet thrombus dynamics—how the platelets clump together. The promising results demonstrated that the automated lab-on-a-chip can accurately control blood flow, deliver and mix drug compounds with blood in seconds, and send the dosed blood to a downstream thrombus assay system.

Arnan Mitchell, PhD, professor of engineering and MNRF director at RMIT, says that existing technologies for testing chemical compounds in blood are highly labor-intensive and time-consuming, limiting how many compounds can be screened at any time. “Our device enables researchers to send hundreds of potential combinations through the system, mixing them with blood extremely rapidly and delivering results in just a few minutes,” he says.

For further information, visit the Royal Melbourne Institute of Technology.

Reference

  1. Szydzik C, Brazilek RJ, Akbaridoust F, et al. Active micropump mixer for rapid antiplatelet drug screening in whole blood. Anal Chem. 2019;91(16):10830–10839; doi: 10.1021/acs.analchem.9b02486.

Featured image:

 Warwick Nesbitt, PhD, Royal Melbourne Institute of Technology (RMIT), with lab on a chip developed at the institute’s micro nano research facility.