New handheld, non-invasive device detects biomarkers for Alzheimer’s, Parkinson’s Diseases

The device relies on electrical rather than chemical detection, which researchers say is easier to implement and more accurate, according to papers in November issue of the Proceedings of the National Academy of Science (https://today.ucsd.edu/story/this-wireless-handheld-non-invasive-device-detects-alzheimers-and-parkinsons-biomarkers).

• The device could be modified to detect biomarkers for other conditions as well
• According to estimates, by 2060, about 14 million Americans were likely to suffer from Alzheimer’s Disease
• The device is the result of his three decades of expertise, as well as his collaboration with researchers globally, including those co-authors in this work from Texas and China: Ratnesh Lal, professor at the UC San Diego Jacobs School of Engineering
• Device likely to hit market in a year

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, Bioengineering, Mechanical Engineering and Materials Science Professor at the UC San Diego Jacobs School of Engineering and one of the paper’s corresponding authors. Funding for the research came from the National Institutes of Health, the UC San Diego and the Chinese Academy of Sciences.

According to estimates, by 2060, about 14 million Americans were likely to suffer from Alzheimer’s Disease. Other neurodegenerative diseases, like Parkinson’s, are also on the rise. At present t t testing methods for Alzheimer’s and Parkinson’s require a spinal tap and imaging tests, including an MRI. As a result, early detection of the disease is difficult, as patients balk at the invasive procedures. Testing is also difficult for patients who are already exhibiting symptoms and have difficulty moving as well as 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, according to the UC communique, Luxe.

Lal wanted to develop a test that would be able to detect amyloid beta and tau peptides – biomarkers for Alzheimer’s – and alpha synuclein proteins – biomarker for Parkinson’s – non invasively, specifically from saliva and urine. He wanted to rely on electrical rather than chemical detection, as he believes it is easier to implement and more accurate. He also wanted to build a device that could wirelessly transmit the test results to the patient’s family and physicians. The device is the result of his three decades of expertise, as well as his collaboration with researchers globally, including those co-authors in this work from Texas and China.

To realize Lal’s vision, he and colleagues adapted a device they developed during the COVID pandemic to detect the spike and nucleoprotein proteins in the live SARS-CoV-2 virus, which they described in PNAS in 2022. That breakthrough had been made possible by chip miniaturization and by large-scale automation of biosensor manufacturing.

According to Alzheimer’s Association,  an estimated 6.7 million people aged 65 and older are living with Alzheimer’s dementia in 2023. Seventy-three percent are aged 75 or older. Of the total US population:  About 1 in 9 people (10.8%) age 65 and older has Alzheimer’s dementia. The percentage of people with Alzheimer’s dementia increases with age: 5.0% of people age 65 to 74, 13.1% of people age 75 to 84, and 33.3% of people age 85 and older have Alzheimer’s dementia. People younger than 65 can also develop Alzheimer’s dementia. Although prevalence studies of younger-onset dementia in the US are limited, researchers believe about 110 of every 100,000 people ages 30-64 years, or about 200,000 Americans in total, have younger-onset dementia. The number and proportion is expected to continue to grow in coming years because the risk of dementia increases with advancing age.

The device described in the 2023 PNAS study, 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 (GFET, with the G standing for graphene) and three electrodes–source and drain electrodes, connected to the positive and negative poles of a battery, to flow electric current, 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, called an aptamer, 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 the 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 were able to detect the specific biomarkers for both conditions with great accuracy, on par with existing state of the art methods. The device also works at extremely low concentrations, meaning that it needs small quantities for samples–down to just a few microliters.

In addition, the tests showed that the device performed well even when the samples analyzed 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 three to arrive at a reliable overall result, according to Luxe.

The technology has been licensed from UC San Diego to a biotechnology startup Ampera Life. It is also planning to test blood plasma and cerebro-spinal fluid with the device, then finally saliva and urine samples.The tests would take place in hospital settings and nursing homes. If those tests go well, Ampera Life plans to apply for FDA approval. The device hopefully will hit the market in a year.