A way forward to reliably triage acute stroke for rapid management

Time to treatment after a stroke is critically important to reduce the chance of brain damage.

Acute stroke is caused by either a sudden bleed (or haemorrhage) or a decrease in blood supply due to a blockage of an artery to the brain (ischaemia). These two distinct types of stroke require completely separate treatment pathways.

A team of researchers at Monash University, Royal Melbourne Hospital and the University of Melbourne have collaborated to develop a small ‘proof-of-concept’ platform with the ability to distinguish between the two types of acute stroke.

Currently, the way to differentiate between these two types of stroke relies on brain imaging, with computed tomography (CT) scanning best able to identify intracranial haemorrhagic stroke, but less so acute ischemic stroke. Brain imaging is for the most part only available in hospital settings and requires significant healthcare resources.

Fortunately, due to modern technology and substantial funding support, a custom-built specialist ambulance vehicle with a CT scanner, known as the Melbourne Mobile Stroke unit, is being piloted across the state for a period of five years, enabling a rapid response for people with suspected stroke.

However, this does not solve the problem of identifying the type of stroke accurately and cost-effectively to assist clinical decision making for the most appropriate treatment pathway.

The study was led by Professor Patrick Kwan, a group leader at the Department of Neuroscience, Central Clinical School and Co-director of Monash Institute of Medical Engineering. “We believe that harnessing the potential of blood-based biomarker detection through medical technology with point-of-care testing would be a feasible solution to ‘bringing the hospital diagnostic facilities straight to the person with an urgent need within minutes’,” said Professor Kwan.

To enable a point-of-care test for the differentiation of stroke types, the team combined their expertise in stroke treatment and biosensor and microfluidic engineering to detect a blood biomarker candidate known as glial fibrillary acidic protein (GFAP). In the acute stroke setting, blood GFAP rises more rapidly and to a higher level in haemorrhagic than ischaemic stroke.

The device uses a novel microfluidic-based magneto-impedance biosensor platform that employs Dynabeads as a magnetic label to capture maximum GFAP molecules. GFAP concentrations were characterised for detection, first using preclinical mouse blood samples, then blood samples provided by patients evaluated with stroke in the Melbourne Mobile Stroke unit tested with the developed microfluidic-based magnetoimpedance biosensor platform.

First author, Dr Abkar Sayad who performed the study during his PhD study under the joint supervision of Professor Kwan and Professor Stan Skafidas, Professor of Nanoelectronics at the University of Melbourne, explained that “our study uses the advantages of magnetoimpedance sensors over conventional sensors, meaning that they produce a higher sensitivity and stability, have a quicker response and are smaller in size, making it the core component of the device.

"Further, we overcame the challenge of an additional external sample processing step by incorporating a microfluidic chip, showing the feasibility of magnetoimpedance biosensor in point of care testing where the device is simply operated by ‘blood in results out’ at one run.”

“The technology allows for the fast and accurate determination of GFAP in a patient blood sample with minimal pre-processing. Importantly the technology has been designed to minimise the interference and confounds from other molecules that may be present in the patient blood sample,” said Professor Skafidas.

One stroke occurs every 19 minutes in Australia, and over 440,000 Australians are living with stroke in 2020, in addition to about 60,000 new patients with acute stroke each year (National Stroke Foundation Report, 2020).

Professor Bernard Yan, a dual Neurologist and Endovascular Neurointerventionaist, at Royal Melbourne Hospital, and one of the authors of the study said, “this rapid blood test will provide access to stroke diagnosis for patients in regional Australia where brain imaging is unavailable. Even more exciting is that doctors could one day treat stroke patients based on test results from a single drop of blood without cumbersome brain imaging.”

The team are now working on optimising and improving the platform to incorporate into a small device to be used by paramedics in the community when attending people with suspected stroke.

Reference:

Sayad, A., Uddin, S. M., Yao, S., Wilson, H., Chan, J., Zhao, H., Donnan, G., Davis, S., Skafidas, E., Yan, B., & Kwan, P. (2022). A magnetoimpedance biosensor microfluidic platform for detection of glial fibrillary acidic protein in blood for acute stroke classification. Biosensors & bioelectronics, 211, 114410. https://doi.org/10.1016/j.bios.2022.114410