Healthcare (Commonwealth Union) – Researchers at the University of Notre Dame have created an innovative automated device capable of diagnosing glioblastoma, an aggressive and currently difficult to treat brain cancer, in under an hour. Typically, glioblastoma patients have a survival time of 12-18 months following diagnosis.
The key element of this diagnostic tool is a biochip that employs electrokinetic technology to identify biomarkers, specifically active Epidermal Growth Factor Receptors (EGFRs). These receptors are overexpressed in certain cancers like glioblastoma and are present in extracellular vesicles.
The EGFRs are a family of receptor tyrosine kinases that play a crucial role in regulating cell growth, differentiation, and survival. The EGFR family consists of four members: EGFR (ErbB1), HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4). These receptors are transmembrane proteins that, upon binding with their specific ligands, form homo- or heterodimers and activate downstream signaling pathways, such as the PI3K/AKT and MAPK/ERK pathways.
Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering at Notre Dame was the lead author of the study that appeared in Communications Biology. He indicated that extracellular vesicles, or exosomes, are unique nanoparticles released by cells and they are much larger 10 to 50 times bigger than a molecule as well as possessing a weak charge. Chang further pointed out that their technology is specially designed to target these nanoparticles, leveraging their characteristics.
The researchers faced a dual challenge: developing a method to differentiate between active and inactive EGFRs and creating a diagnostic technology that is both sensitive and selective in detecting active EGFRs on extracellular vesicles from blood samples.
Researchers developed a biochip incorporating a low-cost electrokinetic sensor, roughly the size of a ballpoint pen’s ball. The small size of extracellular vesicles allows antibodies on the sensor to form multiple bonds with the single vesicle, greatly improving the diagnostic’s sensitivity and selectivity.
Synthetic silica nanoparticles are then used to “report” the presence of active EGFRs on the captured extracellular vesicles, bringing with them a strong negative charge. When these extracellular vesicles with active EGFRs are detected, a voltage shift occurs, signaling the presence of glioblastoma in the patient.
This charge-sensing approach reduces the interference typically seen in current sensor technologies that rely on electrochemical reactions or fluorescence.
“Our electrokinetic sensor allows us to do things other diagnostics cannot,” added Satyajyoti Senapati, a 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 is composed of three key components: an automation interface, a prototype of a portable machine that delivers the necessary materials for conducting the test, and a biochip. While a fresh biochip is needed for each test, the automation interface and the prototype are designed for repeated use.
Each test can be completed in under an hour, utilizing just 100 microliters of blood. The cost of producing each biochip is less than $2.
Although this diagnostic tool was initially developed for glioblastoma, the researchers suggest it could be adapted to detect other types of biological nanoparticles. This adaptability could allow the technology to identify various biomarkers associated with other diseases. Chang mentioned that the team is investigating its potential for diagnosing pancreatic cancer and possibly other conditions such as cardiovascular disease, 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,” explained Chang. “Our hope is that if early detection is more feasible, then there is an increased chance of survival.”
The method maybe considered a form of liquid biopsy as this brain cancer test being extremely aggressive needs faster diagnosis. Since the prognosis for brain cancer when it come to glioblastoma is poor the greater the options in diagnosing will be more helpful for healthcare workers engaged in treatment.
