Medical Design Briefs - February 2024 - 59

Wireless, Handheld, Noninvasive Device Detects
Alzheimer's and Parkinson's Biomarkers
Next steps include testing
saliva and urine samples
with the biosensor.
UCSD
San Diego, CA
An international team of researchers
has developed a handheld, noninvasive
device that can detect biomarkers
for Alzheimer's and Parkinson's
diseases. The biosensor can also transmit
the results wirelessly to a laptop or
smartphone.
The team tested the device on in vitro
samples from patients. The tests showed
the device is as accurate as the state-ofthe-art
testing methods. Ultimately, researchers
plan to test saliva and urine
samples with the biosensor. The device
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. Researchers presented
their findings in the Proceedings of the National
Academy of Science.
" This
portable diagnostic
system
would allow testing at-home and at point
of care, like clinics and nursing homes,
for neurodegenerative diseases globally, "
says 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 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
Medical Design Briefs, February 2024
The biosensor consists of a chip with a highly sensitive transistor made of a graphene layer that is a single atom
thick 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. (Credit: UCSD)
in larger molecules, which in turn form
ion channels in the brain.
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 - noninvasively,
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.
" I am trying to improve quality of life
and save lives, " he says.
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.
www.medicaldesignbriefs.com
n How the Device Is Made and How
It Works
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
59
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Medical Design Briefs - February 2024

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