An international team of researchers has developed a handheld, non-invasive device that can detect biomarkers for Alzheimer’s and Parkinson’s Diseases.
The team tested the device on in vitro samples from patients and showed that it is as accurate as current state-of-the-art methods. Ultimately, researchers plan to test saliva and urine samples with the biosensor.
The device, which transmits the results wirelessly to a laptop or smartphone, could be modified to detect biomarkers for other conditions as well.
The device relies on electrical rather than chemical detection, which researchers say is easier to implement and more accurate.
“This portable diagnostic system would allow testing at-home and at point of care, like clinics and nursing homes, for neurodegenerative diseases globally,” said Ratnesh Lal, a bioengineering, mechanical engineering and materials science professor at the UC San Diego Jacobs School of Engineering and one of the paper’s corresponding authors.
By the year 2060, about 14 million Americans will suffer from Alzheimer’s Disease.
Other neurodegenerative diseases, such as Parkinson’s, are also on the rise. Current state-of-the-art testing methods for Alzherimer’s and Parkinson’s require a spinal tap and imaging tests, including an MRI.
As a result, early detection of the disease is difficult, especially when many patients feel hesitant about invasive procedures. Testing is also difficult for patients who are already exhibiting symptoms and have difficulty moving, along with those who have no early access to local hospitals or medical facilities.
One of the prevailing hypotheses in the field, which Lal has focused on, is that Alzheimer’s Disease is caused by soluble amyloid peptides that come together in larger molecules, which in turn form ion channels in the brain.
Lal wanted to develop a test that could non-invasively detect amyloid beta and tau peptides – biomarkers for Alzheimer’s – and alpha synuclein proteins – a biomarker for Parkinson’s UK awards over £1.8m to fund research He also wanted to rely on electrical rather than chemical detection, as he believes it is easier to implement and more accurate.
Additionally, it was important to Lal that the device could wirelessly transmit the test results to the patient’s family and physicians.
“I am trying to improve quality of life and save lives,” he said.
To realise this vision, he and his colleagues adapted a device they developed during the COVID pandemic to detect the spike and nucleoprotein proteins in the live SARS-CoV-2 virus. That breakthrough had been made possible by chip miniaturisation and by large-scale automation of biosensor manufacturing.
The device consists of a chip with a high-sensitivity transistor, commonly known as a field effect transistor (FET). In this case, each transistor is made of a graphene layer that is a single atom thick, with three electrodes connected to the positive and negative poles of a battery and a gate electrode to control the amount of current flow.
Connected to the gate electrode is a single DNA strand, which serves as a probe that specifically binds to either amyloid beta, tau or synuclein proteins. The binding of these amyloids with their specific DNA strand probe changes the amount of current flow between the source and drain electrode. The change in this current or voltage is the signal used to detect specific biomarkers, like amyloids or COVID-19 proteins.
The research team tested the device with brain-derived amyloid proteins from Alzheimer’s and Parkinson’s deceased patients. The experiments showed that the biosensors could detect the specific biomarkers for both conditions with high accuracy, on par with existing methods. The device also works at extremely low concentrations, meaning that samples need only be a few microliters.
Tests showed that the device performed well even when the samples contained other proteins. Tau proteins were more difficult to detect, but because the device looks at three different biomarkers, it can combine results from all of these to arrive at a reliable overall result.
The technology has been licensed from UC San Diego to a biotechnology startup Ampera Life.
The next steps include testing blood plasma and cerebrospinal fluid with the device, then finally saliva and urine samples. The tests would take place in hospital settings and nursing homes. If these tests go well, Ampera Life plans to apply for FDA approval for the device, hopefully in the next five or six months. The ultimate goal is to bring the device to market in a year.
Funding for the research came from the National Institutes of Health, the University of California San Diego and the Chinese Academy of Sciences.
Researchers presented their findings in the 13 November 2023 issue of the Proceedings of the National Academy of Sciences.