New Liquid Biopsy Detects Glioblastoma Brain Cancer From 100 Microlitres of Blood

Scientists have developed a quicker, less invasive approach to detecting brain cancer than a surgical biopsy.

The new 'liquid biopsy' requires only 100 microlitres of blood. Within an hour, it can identify biomarkers linked with glioblastoma, the most common and deadliest form of brain tumour.

The technique outperforms every currently available glioblastoma test and marker, delivering excellent accuracy. According to the developers of the prototype, it offers "near turn-key functionality".

Created by a US-Australian research team led by scientists at the University of Notre Dame in the US, the proof of concept has limitations but represents a significant advance in diagnosis.

Liquid biopsy targets glioblastoma EGFR biomarkers

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: tiny packages containing proteins, lipids and genetic material from the cells they originated from.

"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 released by cancerous tumour cells, the researchers immersed an ultrasensitive biochip in an untreated blood-plasma sample.

Costing under US$2, the chip includes a minute sensor roughly the size of a ballpoint pen's ball. Its key interface is fitted with antibodies that attract exosomes containing mutated EGFRs.

When EGFRs bind to the biochip, they produce a change in voltage within the plasma solution, generating a high negative charge. This signals possible cancer.

Biochip testing and detection accuracy

During the experiments, researchers used the biochip on clinical blood samples from 20 people with glioblastoma and 10 healthy participants. Each test used one chip.

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

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

"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 can precisely detect and measure 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 – not only for brain cancer.

Limits of the glioblastoma test

However, several issues still need to be resolved.

Mutated EGFRs are associated with more than glioblastoma; they are also connected with conditions such as 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 glioblastoma case. Nor can it determine with certainty which kind of cancer a person has, where in the body it is located, or how far the illness has advanced.

The researchers say a more targeted test will require analysis of 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.