An international team of scientists has created a handheld, non-invasive device that can detect biomarkers for Alzheimer's and Parkinson's diseases. The biosensor can also send test results wirelessly to a laptop or smartphone.
The device was successfully tested on patient in vitro samples, demonstrating accuracy comparable to current state-of-the-art methods. The next phase will be to conduct experiments on saliva and urine samples using this biosensor. Additionally, the device could potentially be used to detect biomarkers for a variety of other conditions.
The researchers say the device relies on electrical detection rather than chemical detection, making it easier to implement and more accurate. Their research results were recently published in the Proceedings of the National Academy of Sciences.
"This portable diagnostic system could enable in-home and point-of-care (such as clinics and nursing homes) testing for neurodegenerative diseases globally," said Ratnesh Lal, professor of bioengineering, mechanical engineering and materials science at UC San Diego's Jacobs School of Engineering and one of the paper's corresponding authors.
Urgent need for early detection
By 2060, approximately 14 million Americans will be affected by Alzheimer's disease. Other neurodegenerative diseases, such as Parkinson's disease, are also on the rise. Current state-of-the-art testing for Alzheimer's and Parkinson's disease requires a spinal tap and imaging tests, including an MRI. As a result, early detection of the disease is difficult as patients are deterred by invasive procedures. Testing is also difficult for patients who are already symptomatic, have limited mobility, and are unable to get to a local hospital or medical facility early enough.
A popular hypothesis in the area where Lal focuses his research is that Alzheimer's disease is caused by soluble amyloid peptides that aggregate into larger molecules and form ion channels in the brain.
Lal hopes to develop a test that can non-invasively detect amyloid beta and tau peptides, biomarkers of Alzheimer's disease, and alpha-synuclein, a biomarker of Parkinson's disease, specifically from saliva and urine. He wants to rely on electronic testing rather than chemical testing because he believes electronic testing is easier to implement and more accurate. He also wants to build a device that can wirelessly transmit test results to patients' families and doctors. The device is the culmination of three decades of expertise and collaboration with researchers around the world, including co-authors on this work from Texas and China.
To realize Lal's vision, he and his colleagues adapted a device they developed during the COVID pandemic to detect spike and nucleoproteins in live SARS-CoV-2 viruses, which they described in 2022 in the Proceedings of the National Academy of Sciences (PNAS). Chip miniaturization and large-scale automation of biosensor manufacturing made this breakthrough possible.
How the equipment is manufactured and works
The device described in the 2023 Proceedings of the National Academy of Sciences (PNAS) study consists of a chip with highly sensitive transistors, commonly known as field-effect transistors (FETs). In this case, each transistor consists of a one-atom-thick graphene layer (GFET, where G stands for graphene) and three electrodes - source and drain (connected to the positive and negative terminals of the battery, used to flow current) and a gate (used to control the amount of current).
Attached to the gate is a DNA strand that serves as a probe that specifically binds to amyloid beta, tau, or synuclein. The binding of these amyloid proteins to their specific DNA strand probes, called aptamers, changes the magnitude of the current between the source and drain. This change in current or voltage is the signal used to detect specific biomarkers, such as amyloid or COVID-19 proteins.
The team tested the device on brain-derived amyloid from Alzheimer's and Parkinson's patients. Experimental results show that the biosensor is able to detect specific biomarkers for both diseases very accurately, on par with existing state-of-the-art methods. The device also works at extremely low concentrations, meaning it requires a small sample volume of just a few microliters.
Furthermore, tests showed that the device works well even if the analyzed samples contain other proteins. Tau protein is more difficult to detect. But because the device detects three different biomarkers, it can combine the results from all three to give a reliable overall result.
The technology has been licensed by UC San Diego to AmperaLife, a biotech startup. Lal is the company's chairman, but his research is not currently funded by the company.
Next steps include using the device to test plasma and cerebrospinal fluid, and eventually saliva and urine samples. Testing will be carried out in hospitals and nursing homes. If these tests go well, AmperaLife plans to apply for FDA approval of the device, which it hopes to receive within the next five or six months. The ultimate goal is to have the device on the market within a year.
Compiled from ScitechDaily