Wireless Handheld Device Detects Alzheimer’s Biomarkers

A multinational team of researchers has created a non-invasive handheld gadget that can identify biomarkers for Alzheimer’s and Parkinson’s diseases. The biosensor can also wirelessly communicate the results to a laptop or smartphone.

The gadget was evaluated on in vitro samples from patients and shown to be as accurate as the state of the art. Eventually, the biosensor will be used to test saliva and urine samples. The technology might also be customized to detect biomarkers for other diseases.

The findings were published in the Proceedings of the National Academy of Sciences on November 13, 2023.

The system detects electrical signals rather than chemical signals, which researchers claim is easier to deploy and more precise.

“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

Alzheimer’s disease will affect around 14 million Americans by 2060. Parkinson’s disease and other neurological disorders are also on the rise. Current cutting-edge testing procedures for Alzheimer’s and Parkinson’s disease necessitate a spinal tap as well as imaging tests, including an MRI. As a result, early disease identification is difficult since patients object to invasive procedures. Patients who are already exhibiting symptoms and have difficulties moving, as well as those who do not have early access to local hospitals or medical facilities, find testing difficult.
One of the dominant hypotheses in the field, on which Lal has concentrated, is that Alzheimer’s Disease is caused by soluble amyloid peptides that aggregate into bigger molecules, which then form ion channels in the brain.

Lal intended to create a non-invasive test that could identify amyloid beta and tau peptides (biomarkers for Alzheimer’s) and alpha-synuclein proteins (biomarkers for Parkinson’s) in saliva and urine. He preferred electrical detection over chemical detection because he believed it is easier to implement and more accurate. He also desired to create a device capable of wirelessly transmitting test findings to the patient’s family and physicians.

The device is the culmination of his three decades of experience, as well as his collaboration with experts throughout the world, including co-authors from Texas and China.

“I am trying to improve quality of life and save lives,” he said.

How the device is made and how it works

The gadget described in the PNAS research from 2023 is made up of a chip having a high-sensitivity transistor known as a field effect transistor (FET). Each transistor in this case is made of a single atom thick graphene layer (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.

A single DNA strand is connected to the gate electrode and acts as a probe, particularly binding to amyloid beta, tau, or synuclein proteins. The interaction of these amyloids with their unique DNA strand probe, known as an aptamer, alters the amount of current flowing between the source and drain electrodes. The signal utilized to identify certain biomarkers, such as amyloids or COVID-19 proteins, is a change in this current or voltage.

The gadget was tested using brain-derived amyloid proteins from deceased Alzheimer’s and Parkinson’s patients. The experiments demonstrated that the biosensors could identify the specific biomarkers for both situations with high accuracy, comparable to existing state-of-the-art approaches. The device also operates at extremely low concentrations, which means it only requires a few microliters of sample.

Furthermore, the experiments revealed that the gadget worked well even when the samples tested contained additional proteins. Tau proteins were harder to identify. However, because the gadget examines three independent biomarkers, it may aggregate the results of all three to produce a reliable overall result.

Ampera Life, a biotechnology business, has licensed the technology from UC San Diego. Lal is the company’s chairman, yet he receives no financial assistance for his research.

The device will next be used to test blood plasma and cerebrospinal fluid, followed by saliva and urine samples. The examinations would be conducted in hospitals and nursing homes. If the testing goes well, Ampera Life intends to submit an application to the FDA for device approval within the next five to six months. The ultimate goal is to have the device available for purchase within a year.

For more information: In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2311565120.