From rapid diagnosis of heart attacks to screening bleeding disorders, tiny devices designed to handle the complexities of blood could be the future of pathology.
When you’re working with a fluid as hypersensitive as blood, it pays to have specialists on board.
“Blood isn’t straightforward. It’s very sensitive to artificial surfaces so it will stick like crazy to things, you get clotting all over the place,” says RMIT biochemist Dr Warwick Nesbitt.
“This affects the results, making most micro devices unsuitable for clinical use.
“To date, the development of small blood handling devices has largely been driven by engineers that have little insight into the biology of blood.
“That’s where we come in.”
A lab on a postage stamp
Nesbitt and his team at RMIT’s Micro Nano Research Facility (MNRF) and the Australian Centre for Blood Diseases are at the crossroads of engineering and biomedical science.
Their aim? To miniaturise the complex blood-handling features of a pathology lab onto a tiny chip, the size of a postage stamp.
Along with researchers at Monash University and the University of Melbourne, and clinicians at the Alfred Hospital’s Department of Clinical Haematology, the team has successfully developed new microfluidic technologies that are being used in a myriad of ways to help solve clinical challenges in haematology.
These range from more accurate diagnostic tools for blood disorders, to improving our understanding of how platelets work and developing devices that can slash the time it takes to verify if someone has suffered a heart attack.
The work was recently boosted with a $657,000 grant from the National Health and Medical Research Council (NHMRC) to support the development of a microfluidic platelet analyser that can indicate whether blood clots effectively.
The microfluidic chips being developed by the team contain tiny channels, pumps, valves and processors, enabling precise and flexible manipulation of fluids.
The chips are fast, portable and able to handle vast quantities of tiny processing elements. Importantly, they are also cost-effective to produce and can be easily mass manufactured.
When combined with a highly sensitive photonic sensor, for biochemical analysis, the technology effectively becomes a miniature laboratory – a lab-on-a-chip – but one that needs no specialist training to use.
“Because whole blood is so complex, most blood diagnostic tests tend to involve some form of processing, such as spinning out red blood cells,” Nesbitt says.
“Pathology lab tests are technically demanding and expensive. You need a highly-trained medical scientist that is experienced in blood separation techniques and analysis to ensure consistency of results.
“Our ultimate aim is to make lab-on-a-chip devices that an unskilled operator can use, that can either do the processing inside the device or work with blood taken straight from patients.
“This is particularly important for regional areas, where emergency clinics with no in-house pathology services can face long delays in waiting for results.”
Precision and reliability
Nesbitt and the team at the MNRF develop micro devices that can be used for three key aspects of blood: bleeding, clotting and detecting biomarkers.
The researchers have worked on the diagnosis and monitoring of the most common genetic bleeding disorder, Von Willebrand disease (VWD).
Current testing of VWD involves laboratory-based assays along with clinical assessment. In addition certain forms of the disease can be difficult to diagnose.
The RMIT team’s proof-of-concept trial showed their tailored micro device could detect the particular forms of the disease that are most difficult to spot with standard tests.
“Blood from healthy people behaves differently to the blood of someone with VWD,” Nesbitt explains.
“If the blood is from a healthy person, the platelets clump together to form a mini thrombus.
“They don’t clump in someone with VWD and that’s what we can measure with great precision - exactly how much the platelets cluster together.”
In future, the team is hoping to use the same device to detect changes in the way platelets function in people with diabetes, metabolic syndrome and acute coronary syndrome; conditions that make patients prone to platelet-dependent cardiovascular diseases.
The researchers have also had promising early results in the development of a device to sensitively detect cardiac troponin, a clinical biomarker for heart attacks.
“Clinicians test blood for troponin when a patient comes into emergency suffering signs of heart attack, but it can take some time for results to come back from pathology,” Nesbitt says.
“There are faster bedside tests on the market but they’re not always reliable and there is a push for more reliable point-of-care tests.
“We’re working on a point-of-care device that brings together a sensiitve photonic sensor and a microfluidic system to give reliable results in minutes.”
Ear to the ground
Nesbitt joined RMIT three years ago as a Vice-Chancellor’s Senior Research Fellow and began to dive deep into the challenge of developing blood-compatible micro devices.
Embedded with clinicians at the Alfred, he often gets his research challenges straight from the source.
“I spend most of my week working alongside clinicians so of course we’re always talking about the problems they face, whether it’s diagnostic tests that are old and unreliable or the lack of precision tools for the work they’re trying to do,” he says.
“I take that back to the lab and we start working on a solution.
“Whatever we’re looking at, we know there’s a need. And you just don’t get that kind of clinical insight without that day-to-day interaction with the people who are at the coalface.”
Story: Gosia Kaszubska