Device measures alpha-synuclein at very low concentrations
Portable system detects biomarkers for Parkinson's, other neurological disorders
Scientists have developed a handheld device that can be used to measure levels of biomarkers for Parkinson’s disease and other neurological disorders.
“This portable diagnostic system would allow testing at-home and at point of care, like clinics and nursing homes, for neurodegenerative diseases globally,” Ratnesh Lal, PhD, said in a press release. Lal is a professor at the University of California San Diego and co-author of the study.
The technology for the sensor has been licensed from the University of California San Diego to a biotechnology startup called Ampera Life. If ongoing tests show consistent positive results, the company plans to ask the U.S. Food and Administration to authorize the device in the next few months, with the goal of bringing it to market in about a year.
The device’s development was described in the journal PNAS, in the study “In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor.”
Parkinson’s disease is marked by clumps of the protein alpha-synuclein in the brain, which are toxic to brain cells and are thought to play a central role in causing the disease. Toxic protein clumps also are thought to be involved in Alzheimer’s disease, which is marked by clumps of the proteins amyloid-beta and tau.
These toxic proteins can be detected in the fluid that surrounds the brain (called the cerebrospinal fluid or CSF), but collecting this fluid is invasive and arduous for patients. Here, an international team of scientists reported on their work to advance a test that can measure these disease biomarkers in less invasive ways.
“Our goal is to detect/diagnose physiological [amyloid beta], tau, and [alpha-synuclein] from saliva, urine, and other biofluids,” the scientists wrote.
To this end, the researchers adapted technology they developed previously to help detect SARS-CoV-2, the virus that causes COVID-19.
The technology basically consists of a thin layer of graphene attached to three electrodes. Two electrodes attached to the positive or negative ends of a battery, and a third so-called gate electrode allows an electrical current to flow between the other two electrodes.
Attached to the gate electrode are specialized probes designed to detect a particular target molecule. When the probe binds to its target, it changes the amount of electricity that can flow across the electrodes. This change in electric current can be detected by a computer and extrapolated to calculate the concentration of the target molecule.
For its molecular probes, the system uses aptamers, which are single DNA strands folded like origami into a specific shape that allows them to bind to the target.
Detecting alpha-synuclein, tau and beta-amyloid
In tests using synthetic proteins, the researchers demonstrated this setup could detect alpha-synuclein, tau, and beta-amyloid — two proteins associated with Alzheimer’s disease — using aptamers targeting each of the three proteins. For alpha-synuclein specifically, the system could detect the protein at concentrations as low as 10 femtomolar (less than a trillionth of a mole).
Proof-of-concept tests using solutions diluted with other proteins or extracts from autopsied brains of people with neurological disease also indicated that the system could detect these target proteins even in the presence of other proteins that are found in biological samples.
“This makes the biosensor a strong candidate for diagnostics as it will limit nontarget binding and false-positive results and will also allow for greater lower limits of detection in human samples,” the researchers wrote, noting that they are currently working toward tests of the system in more clinically relevant samples like saliva and urine.