Researchers develop affordable and fast test device for brain cancer

The device features a biochip that uses electrokinetic technology to detect biomarkers, or active Epidermal Growth Factor Receptors (EGFRs), which are overexpressed in certain cancers such as glioblastoma and found in extracellular vesicles.

“Extracellular vesicles or exosomes are unique nanoparticles secreted by cells. 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,” Hsueh-Chia Chang, Bayer Professor of Chemical and Biomolecular Engineering at Notre Dame, Indiana, and lead author of the study, said in a statement.

The challenge for the researchers was to develop a process that could distinguish between active and non-active EGFRs and create a diagnostic technology that was sensitive, yet selective, in detecting active EGFRs on extracellular vesicles from blood samples.

To do this, the team created a biochip that uses an inexpensive, electrokinetic sensor about the size of the ball in a ballpoint pen. Due to the size of the extracellular vesicles, antibodies on the sensor can form multiple bonds to the same extracellular vesicle, which the researchers said significantly enhances the sensitivity and selectivity of the diagnostic tool.

Synthetic silica nanoparticles ‘report’ the presence of active EGFRs on the captured extracellular vesicles, while bringing a high negative charge. When extracellular vesicles with active EGFRs are present, a voltage shift can be seen, indicating the presence of glioblastoma in the patient.

The researchers said that this charge-sensing strategy minimises interference common in current sensor technologies that use electrochemical reactions or fluorescence.

“Our electrokinetic sensor allows us to do things other diagnostics cannot,” said Satyajyoti Senapati, research associate professor of chemical and biomolecular engineering at Notre Dame and co-author of the study. “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.”

The device includes a total of three parts: an automation interface, a prototype of a portable machine that administers materials to run the test, and the biochip. Each test requires a new biochip, but the automation interface and prototype are reusable.

Running one test takes under an hour, requiring only 100 microliters of blood. The researchers added that each biochip costs under $2 in materials to manufacture.

Although this diagnostic device was developed for glioblastoma, the researchers said it can be adapted for other types of biological nanoparticles, which opens up the possibility for the technology to detect a number of different biomarkers for other diseases. Chang said the team is exploring the technology for diagnosing pancreatic cancer and potentially other disorders such as cardiovascular disease, dementia and epilepsy.

Blood samples for testing the device were provided by the Centre for Research in Brain Cancer at the Olivia Newton-John Cancer Research Institute in Melbourne, Australia, and the study was funded by the National Institutes of Health Common Fund.

The study, published in Communications Biology, can be read in full here.