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Researchers at the University of Notre Dame have developed a new automated device that can diagnose glioblastoma, a fast-growing, incurable brain tumor, in less than an hour. Patients with glioblastoma survive an average of 12 to 18 months after diagnosis.
At the heart of this diagnostic is a biochip that uses electrokinetic technology to detect a biomarker, namely active epidermal growth factor receptor (EGFR), which is overexpressed in certain cancers such as glioblastoma and is found in extracellular vesicles.
“Extracellular vesicles, or exosomes, are unique nanoparticles secreted by cells. They are 10 to 50 times larger than molecules and have a weak charge. Our technology takes advantage of the properties of these nanoparticles and was designed specifically for these nanoparticles,” said Xue-Chia Zhang, Bayer Professor of Chemical and Biomolecular Engineering at the University of Notre Dame and lead author of the diagnostics study published in Communications Biology.
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The challenge for the researchers was two-fold: to develop a process that could distinguish active from inactive EGFR, and to create a diagnostic technique that could sensitively and selectively detect active EGFR on extracellular vesicles in blood samples.
To achieve this, the researchers developed a biochip that uses an inexpensive electrokinetic sensor about the size of a ballpoint pen. The size of the extracellular vesicles allows the antibodies on the sensor to form multiple bonds to the same extracellular vesicles. This method significantly improves the sensitivity and selectivity of the diagnosis.
The synthetic silica nanoparticles then “report” the presence of active EGFR on the captured extracellular vesicles, resulting in a high negative charge. If extracellular vesicles containing active EGFR are present, a voltage shift will be seen, 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 something that other diagnostics cannot,” said Satyajyoti Senapati, a research associate professor of chemical and biomolecular engineering at Notre Dame and co-author of the study. “Because our sensor is not affected by other particles or molecules, we can directly inject blood without pre-treatment to isolate extracellular vesicles. It produces less noise and is more sensitive to disease detection than other techniques.”
The device consists of three parts: an automation interface, a prototype of a portable machine that administers the materials to perform the test, and a biochip. Although a new biochip is required for each test, the automation interface and the prototype can be reused.
Each test takes less than an hour and requires just 100 microliters of blood, and the materials cost less than $2 per biochip.
Although the diagnostic device was developed for glioblastoma, the researchers say it could be applied to other types of biological nanoparticles, opening up the possibility that the technology could detect a range of biomarkers for other diseases. Chang said the team is looking to apply the technology to diagnose pancreatic cancer, as well as other conditions such as cardiovascular disease, dementia and epilepsy.
“While our technique is not specific to glioblastoma, the disease's high mortality rate and lack of early screening tests made it a particularly appropriate place to start,” Chang said. “The hope is that earlier detection will improve the chances of survival.”
Reference: Maniya NH, Kumar S, Franklin JL, et al. “Anion exchange membrane sensor detects EGFR and its activation state in plasma CD63 extracellular vesicles from glioma patients.” Commun Biol. 2024;7(1):677. doi: 10.1038/s42003-024-06385-1
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