Novel biochip diagnoses deadly brain cancer in under an hour

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.

At 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 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 larger than a molecule -; and they have a weak charge. Our technology is specifically designed for these nanoparticles and uses their properties to our advantage.”

Hsueh-Chia Chang, lead author of the study and Bayer professor, chemical and biomolecular engineering, University of Notre Dame

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

To do this, researchers have created a biochip that uses a cheap, electrokinetic sensor the size of a ball in 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 diagnostics.

Then, synthetic silica nanoparticles “report” the presence of active EGFRs on the captured extracellular vesicles, while carrying 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 the interference common to 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 professor of chemical and biomolecular engineering at Notre Dame and co-author of the study. “We can load blood directly without any pretreatment to isolate the extracellular vesicles because our sensor is not affected by other particles or molecules. It is low-noise and makes ours more sensitive to disease detection than other technologies.”

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

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

Although this diagnostic device was developed for glioblastoma, the researchers say it could be adapted for 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 investigating the technology for diagnosing pancreatic cancer and possibly other conditions such as cardiovascular disease, dementia and epilepsy.

“Our technique is not specific for glioblastoma, but it was particularly appropriate to begin with because of its lethality and lack of early screening tests,” Chang said. “Our hope is that if early detection is more feasible, there will be a greater chance of survival.”

Blood samples for testing the device were provided by the Center for Research in Brain Cancer 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 from the Olivia Newton-John Cancer Research Institute and La Trobe University. The study was funded by the National Institutes of Health Common Fund.

Chang and Senapati are affiliated with the Berthiaume Institute for Precision Health at Notre Dame, the Harper Cancer Research Institute and NDnano.