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Biocompatible ‘lab on a chip’ shows potential in development of antiplatelet therapies
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A novel biocompatible “lab-on-a-chip” device may help accelerate the discovery and development of new antiplatelet therapies, according to research published in Analytical Chemistry.
“Blood is extremely sensitive to artificial surfaces and clots very easily, so blood-handling technologies must be equally sensitive,” Warwick S. Nesbitt, PhD, senior lecturer at the School of Engineering of RMIT University, and leader of the Haematology Microplatforms Group of Australian Centre for Blood Diseases at Monash University in Melbourne, Australia, said in a press release. “We have 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 antiplatelet treatments to improve the health and well-being of millions around the world.”
Nesbitt and colleagues conducted a proof-of-concept study of their “microlab” device — which researchers said shrinks a pathology lab onto a chip the size of a postage stamp — to assess how dosing blood with select small molecule inhibitors may affect platelet thrombus dynamics.
According to study results, the automated “lab-on-a-chip” technology appeared to accurately control blood flow, deliver and combine drug compounds with blood in seconds, and successfully deliver the dosed blood to a thrombus assay system.
Nesbitt spoke with HemOnc Today about what prompted the development of this device, the results of the study and plans for additional research.
Question: What prompted the development of this micro fluidic device?
Answer: Current antiplatelet therapies, although effective, suffer from a narrow therapeutic window due to bleeding complications. We are looking to identify and develop new antiplatelet drugs that minimize associated bleeding. One approach is to screen drug libraries for candidate drugs that are selective for the mechanical effects of blood flow on platelet function. To do this, we required a platform that allows for rapid screening, but also for dynamic blood flow regulation in vitro. We therefore are in the process of developing a multiplexed microfluidic approach that utilizes specially designed micropumps and microchannels.
Q: What makes this unique from anything else available?
A: Although microfluidic approaches have been used to investigate the effects of blood flow on platelet function and thrombosis, most, if not all, are limited with respect to scalability and throughput. In addition, most utilize large, bulky external mechanical pumps to deliver blood to the microfluidic chips. By integrating a micropump system into chip design, we can minimize the amount of blood needed for experimentation. In addition, because the micropumps are part of the microfluidic device, we have very rapid control over the rate of blood flow in the device. Importantly, the micropumps also act as very fast mixers, which has enabled us to inject drugs into the blood flow on the chip and examine how these drugs affect platelet function across rapid time scales.
Q: Can you describe how it works?
A: The microfluidic device uses a series of very small microscale peristaltic pumps and gates to control the:
delivery of blood samples to the device;
velocity of blood flow in the device to mimic the conditions present at sites of arterial disease processes;
injection and delivery of drugs into the blood flow; and
rate and extent of mixing of the drug molecules with the blood sample.
The device also incorporates a segment that is coated with type 1 collagen. Delivery of the blood sample to this collagen-coated surface triggers platelet thrombus formation that can be monitored in real time using a microscope.
Q: How did you conduct the research?
A: The research project forms part of a larger collaboration between the School of Engineering, RMIT University and Australian Centre for Blood Diseases at Monash University. Development and fabrication of the device was carried out within the MicroNano Research facility at RMIT, and the blood, biological testing and validation was carried out in the Australian Centre for Blood Diseases laboratories.
Q: What did you find ?
A: Our work demonstrates a novel prototype device that can very rapidly analyze the effect of candidate drug molecules on platelet function and thrombosis. The described device and methods are a stepping stone toward large-scale, high-throughput drug-to-blood screening systems, with a particular focus on the development of new antiplatelet therapies to treat heart attack and stroke.
Q: What challenges have you run into and how do you plan to overcome them?
A: A major challenge in the development of microfluidic blood-handling devices is the ability to handle blood samples without adversely affecting blood and blood cell functions. This requires careful consideration of both materials and functional (mechanical) blood compatibility of these devices.
Q: Do you have plans for additional research on this?
A: The published work forms part of a much larger program of work to develop novel “lab-on-a-chip” and “organ-on-a-chip” technologies for application to basic, preclinical and clinical research in hematology. This work would not be possible without the multidisciplinary team of collaborators across engineering at RMIT, biomedical research at Australian Centre for Blood Diseases and clinical hematology at Alfred Hospital and the ongoing support of the National Health and Medical Research Council and RMIT and Monash universities. – by Jennifer Southall
Reference:
Szydzik C, et al. Anal Chem. 2019;doi:10.1021/acs.analchem.9b02486.
For more information:
Warwick S. Nesbitt, PhD, can be reached at Australian Centre for Blood Diseases at Monash University, Level 1, Walkway, via The Alfred Centre, 99 Commercial Road, Melbourne, 3004, Australia; email: warwick.nesbitt@rmit.edu.au.
Disclosure: Nesbitt reports no relevant financial disclosures.