New Liquid Biopsy Detects Glioblastoma Biomarkers in Blood Within an Hour

Scientists have developed a new approach for detecting brain cancer that is quicker and less invasive than a surgical biopsy.

Just 100 microlitres of blood are required for this new ‘liquid biopsy’, which can identify biomarkers linked with glioblastoma - the most common and deadliest form of brain tumour - in under an hour.

The technique outperforms every existing glioblastoma test and marker, delivering excellent accuracy. According to the prototype’s developers, it has "near turn-key functionality".

Liquid biopsy for glioblastoma detection

The advance comes from a US-Australian research group led by scientists at the University of Notre Dame in the US. Although their proof of concept has limitations, it represents an important diagnostic advance.

The test works by detecting mutated blood biomarkers known as epidermal growth factor receptors (EGFRs), which are overexpressed in some cancers, including glioblastoma.

These biomarkers are enclosed within extracellular vesicles: small parcels containing proteins, lipids and genetic material from the cells that produced them.

"Extracellular vesicles or exosomes are unique nanoparticles secreted by cells," explains biomolecular engineer Hsueh-Chia Chang from Notre Dame.

"They are big – 10 to 50 times bigger than a molecule – and they have a weak charge. Our technology was specifically designed for these nanoparticles, using their features to our advantage."

To identify molecules shed by cancerous tumour cells, the researchers immersed a highly sensitive biochip in an untreated blood-plasma sample.

The chip costs under US$2 and includes a minute sensor roughly the size of the ball in a ballpoint pen. Its key interface contains antibodies that attract exosomes carrying mutated EGFRs.

When these EGFRs bind to the biochip, they cause a voltage shift in the plasma solution, producing a high negative charge. This signals the possible presence of cancer.

Biochip accuracy and testing

In trials, the biochip was assessed using clinical blood samples from 20 people with glioblastoma and 10 healthy individuals, with one chip used for every test.

In the end, the liquid biopsy identified cancer biomarkers with excellent accuracy and a very low p value, suggesting that the test is highly reproducible.

"Our electrokinetic sensor allows us to do things other diagnostics cannot," explains biomolecular engineer Satyajyoti Senapati from Notre Dame.

"We can directly load blood without any pretreatment to isolate the extracellular vesicles because our sensor is not affected by other particles or molecules. It shows low noise and makes ours more sensitive for disease detection than other technologies."

Senapati and colleagues report that, in experiments, the biochip accurately detects and quantifies exosome concentrations even at levels as low as 0.01 percent.

The team argues that this could have "great implications" for cancer research, biomarker discovery and disease monitoring - extending beyond brain cancer.

Limits of the glioblastoma test

However, several issues still need to be resolved.

Mutated EGFRs are associated not only with glioblastoma, but also with other conditions, including colorectal cancers.

"Therefore, such an EGFR active and total signature might not necessarily indicate the presence of glioblastoma specifically," the authors write.

"Likewise, patients with glioblastoma can have amplified or mutated EGFR but can also have non-EGFR driven forms of the disease."

Consequently, the test cannot diagnose every possible case of glioblastoma. Nor can it definitively identify the type of cancer a person has, its location in the body, or how far the disease has progressed.

To develop a more specific test, the researchers say they must examine larger groups of glioblastoma patients to establish which blood biomarkers distinguish them.

"The current diagnostic platform can be scaled up for such large-library testing of untreated plasma from a large cohort of cancer patients to establish specific profiles for different cancers at different stages," the researchers conclude.

The study was published in Communications Biology.