Rapid Liquid Biopsy Test for Glioblastoma Developed by Notre Dame Team


Glioblastoma brain cancer, CT scan
Credit: DR P. MARAZZI/SCIENCE PHOTO LIBRARY/Getty Images

A team of investigators from Notre Dame has developed a blood-based test that they say can diagnose glioblastoma in less than an hour. The new diagnostic uses an electrokinetic technology that is capable of detecting epidermal growth factor receptors (EGFRs), which are known to be overexpressed in glioblastoma and other cancers and found in extracellular vesicles. The team’s research is published in the journal Communications Biology.

“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,” said lead author Hsueh-Chia Chang, PhD, a professor of chemical and biomolecular engineering at Notre Dame.

For their research, the investigators needed to develop an approach that could first distinguish between active and non-active EGFRs and then create a technology capable of identifying these differences. The solution was an electrokinetic sensor about the size of the ball on a ballpoint pen. As described by the researchers: “Due to the size of the extracellular vesicles, antibodies on the sensor can form multiple bonds to the same extracellular vesicle. This method significantly enhances the sensitivity and selectivity of the diagnostic.”

Synthetic silica nanoparticles are employed in the process to identify the presence of active EGFRs on the extracellular vesicles captured on the sensor. When the extracellular vesicles have active EGFRs, the sensor can identify a shift in voltage that indicates the presence of glioblastoma in the sample from the patients. The team noted that their approach minimizes the interference common in other current sensors that employ either electrochemical reactions or fluorescence.

Satyajyoti Senapati, PhD, a research associate professor of chemical and biomolecular engineering and co-author of the study, noted: “Our electrokinetic sensor allows us to do things other diagnostics cannot. 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 diagnostic device comprises three components: an automation interface, a portable machine prototype for administering test materials, and the biochip. Each test requires a new biochip—which costs less than $2 each to produce—but the automation interface and prototype are reusable. The test process reportedly takes less than an hour and requires only 100 microliters of blood.

While the team focused their development on a fast, inexpensive, blood-base test for glioblastoma, the most common and deadly form of brain cancer, it could very easily be adapted for use in other diseases for detecting similar biomarkers. Other potential applications could be found for diagnosing pancreatic cancer, as well as cardiovascular diseases, dementia, and epilepsy.

“Our technique is not specific to glioblastoma, but it was particularly appropriate to start with it because of how deadly it is and the lack of early screening tests available,” said Chang. “Our hope is that if early detection is more feasible, then there is an increased chance of survival.”



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