Researchers develop rapid, affordable blood test for brain cancer

Researchers at the University of Notre Dame have developed a new automated device that can diagnose glioblastoma, a fast-growing and incurable brain cancer, in less than an hour. The average glioblastoma patient survives 12 to 18 months after diagnosis.

The heart of the diagnostic is a biochip that uses electrokinetic technology to detect biomarkers, or active epidermal growth factor receptors (EGFRs), which are overexpressed in some cancers such as glioblastoma and found in extracellular vesicles.

“Extracellular vesicles, or exosomes, are unique nanoparticles secreted by cells. They are large—10 to 50 times larger than a molecule—and have a low charge. Our technology was specifically designed for these nanoparticles, using their characteristics to our advantage,” said Hsueh-Chia Chang, Bayer Professor of Chemical and Biomolecular Engineering at Notre Dame and lead author of the diagnostic study published in Biology of communications.

The challenge for the researchers was twofold: to develop a process capable of distinguishing between active and non-active EGFRs, and to create a diagnostic technology that is sensitive but selective in detecting active EGFRs on extracellular vesicles from blood samples.

To do this, the researchers created a biochip that uses an inexpensive electrokinetic sensor about the size of a ballpoint pen. Due to the size of the extracellular vesicles, antibodies on the sensor can form multiple bonds with the same extracellular vesicle. This method significantly improves the sensitivity and selectivity of the diagnosis.

The synthetic silica nanoparticles then “signal” the presence of active EGFRs on the captured extracellular vesicles, while providing a high negative charge. When extracellular vesicles with active EGFRs are present, a voltage shift can be observed, indicating the presence of glioblastoma in the patient.

This charge sensing strategy minimizes interferences common in current sensor technologies that use electrochemical reactions or fluorescence.

“Our electrokinetic sensor allows us to do things that other diagnostics can’t do,” said Satyajyoti Senapati, associate research professor of chemical and biomolecular engineering at Notre Dame and co-author of the study. “We can directly load the blood without any pretreatment to isolate extracellular vesicles because our sensor is not affected by other particles or molecules. It has low noise, making ours more sensitive to disease detection than other technologies.”

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

A test takes less than an hour and requires only 100 microliters of blood. Each biochip costs less than $2 in materials to manufacture.

While this diagnostic device was developed for glioblastoma, the researchers say it can be adapted to other types of biological nanoparticles. This 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 to diagnose pancreatic cancer and potentially other disorders such as cardiovascular disease, dementia and epilepsy.

“Our technique is not specific to glioblastoma, but it was particularly relevant to start with it because of its mortality and the lack of available early detection tests,” Chang said. “We hope that if early detection is easier, the chances of survival will be higher.”

Blood samples to test the device were provided by the Brain Cancer Research Centre at the Olivia Newton-John Cancer Research Institute in Melbourne, Australia.

In addition to Chang and Senapati, other collaborators include former Notre Dame postdocs Nalin Maniya and Sonu Kumar; Jeffrey Franklin, James Higginbotham and Robert Coffey of Vanderbilt University; and Andrew Scott and Hui Gan of the Olivia Newton-John Cancer Research Institute and La Trobe University.