'Fishing' for biomarkers
Researchers have developed a broadly applicable nano-sensor capable of single-molecule precision

Date:
March 20, 2023
Source:
Syracuse University
Summary:
Researchers have devised a tiny, nano-sized sensor capable of
detecting protein biomarkers in a sample at single-molecule
precision. Fittingly coined as 'hook and bait,' a tiny protein
binder fuses to a small hole created in the membrane of a cell --
known as a nanopore -- which allows ionic solution to flow through
it. When the sensor recognizes a targeted molecule, the ionic flow
changes. This change in flow serves as the signal from the sensor
that the biomarker has been found.


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FULL STORY ========================================================================== While a popular hobby for many, fishing is also a pastime full of
uncertainty.

Each time you have something on the line, you can never be completely sure
what type of fish you've hooked until you pull it out of the water. In
a similar way, scientists "fishing" for biomarkers -- molecules whose
health care applications include signaling for the presence of cancer --
in biofluids such as blood can also encounter unpredictability. Finding
a specific protein biomarker in a pool of thousands is like trying to
catch a particular fish species in the vast ocean.


========================================================================== Luckily, a team of researchers from Syracuse University's College of Arts
and Sciences (A&S), SUNY Upstate Medical University, Ichor Therapeutics,
and Clarkson University have devised a tiny, nano-sized sensor
capable of detecting protein biomarkers in a sample at single-molecule precision. Fittingly coined as "hook and bait," a tiny protein binder
fuses to a small hole created in the membrane of a cell -- known as a
nanopore - which allows ionic solution to flow through it. When the
sensor recognizes a targeted molecule, the ionic flow changes. This
change in flow serves as the signal from the sensor that the biomarker
has been found.

"These nanopores are equipped with hooks that pull certain protein
biomarkers from a solution," says Liviu Movileanu, professor of physics
in A&S, who co- authored the study along with postdoctoral researcher
Mohammad Ahmad. "By fishing them from the solution quickly and accurately,
we can better identify and quantify protein biomarkers that are associated
with various hematological malignancies and solid tumors." The team's
latest research, published in Nature Communications, addresses previous challenges that existed in making this technology generalizable. Their
new findings formulate a sensor design architecture that can be applied
to a broad range of protein targets.

Combining Innovative Technologies For the first time, the team coupled
nanopore technology with antibody mimetic technology -- artificially
designed protein scaffolds that bind and interact with a specific
biomarker and behave like antibodies. Cells inside the body design their
own antibodies which bind to and eliminate unwanted substances.

When it comes to therapeutics, scientists engineer small proteins to
penetrate cells and stimulate the production of antibodies which target specific pathogens like viruses or bacteria.

"Researchers design the scaffolds using established scaffolds from mother nature and adapt them using evolutionary mutagenesis -- where they scan billions of DNA mutations until they find some that interact strongly
with a specific protein," says Movileanu, whose work on the project
was supported by a $1.2 million grant from the National Institutes
of Health. "Creating highly specific protein detection technologies
will address these demands and also accelerate discoveries of new
biomarkers with potential consequences for the progression of pathological conditions." According to Movileanu, in addition to working in a clean solution, the sensor is also highly effective in complex biofluids,
like blood serum, that contain numerous antibodies.

"Essentially you have a very specific hook that targets a very specific protein," he explains. "Since the signal encodes the exact protein that
you are targeting, this technique does not have false positives, making
it practical for biomedical diagnostics." To validate their findings,
the team tested their hypothesis using a blood serum sample. With their technology, they were able to identify and quantify epidermal growth
factor receptor (EGFR), a protein biomarker in various cancers. In
addition, numerous calibrations of the sensors were conducted using
other biophysical techniques.

At the Forefront of Diagnosis While their paper provides a concept
prototype, Movileanu says the project paves the way for broad
applications. For example, by integrating the sensors into nanofluidic
devices, this technology would allow scientists to test for many
different biomarkers at once in a specimen, providing a fundamental
basis for biomarker detection in complex biofluids.

"The future of medicine won't rely as much on imaging and biopsies
when diagnosing cancers," says Movileanu. "Instead, researchers will
use nano-sensor technology, like what we are developing in our lab, to
test blood samples for the presence of various biomarkers associated with different cancers. This research is critical to the future of prognostics, diagnostics and therapeutics."
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========================================================================== Story Source: Materials provided by Syracuse_University. Original written
by Dan Bernardi.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. M. Ahmad, J.-H. Ha, L.A. Mayse, M. Presti, A.J. Wolfe, K.J. Moody,
S.

Loh, L. Movileanu. A Generalizable Nanopore Sensor for Highly
Specific Protein Detection at Single-Molecule Precision. Nature
Communications, 2023 DOI: 10.1038/s41467-023-36944-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/03/230320143814.htm

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