Graphene binding pain receptor leads to biosensor breakthrough

Researchers from the University of Pennsylvania have led an effort to
create an artificial chemical sensor based on the mu-opiod receptor,
which is critical in the action of painkillers and anaesthetics. The devices,
which could be useful in drug development and a variety of diagnostic
tests, produce an electrical response to receptor activation that can be
read out by computer.

By attaching a modified version of the mu-opioid receptor to strips
of graphene, they have developed a technique that could be applied to
detection of a wide range of biologically relevant chemicals.
The study, published in Nano Letters, was led by Charlie Johnson,
director of Penn’s Nano/Bio Interface Center in collaboration with
Renyu Liu, assistant professor of anaesthesiology at the Perelman
School of Medicine, and Jeffery Saven, professor of chemistry in Penn
Arts & Sciences. The Penn team also worked with researchers from the
Seoul National University in South Korea.

Johnson’s group has extensive experience attaching biological
components to nanomaterials for use in chemical detectors. Previous
studies have involved wrapping carbon nanotubes with singlestranded
DNA to detect odours related to cancer, and attaching
antibodies to nanotubes to detect the presence of the bacteria
associated with Lyme disease.

The groups of Saven and Liu used computational techniques to
redesign the mu-opioid receptor so that it could be readily grown and
attached directly to graphene, thereby opening up the possibility of
mass-producing biosensor devices that utilise the receptor.
“Due to the challenges associated with isolating these receptors
from their membrane environment without losing functionality, the
traditional methods of studying them involved indirectly investigating
the interactions between opioid and the receptor via radioactive
or fluorescent labelled ligands, for example,” said Liu. “This multidisciplinary
effort overcame those difficulties, enabling us to investigate
these interactions directly in a cell-free system without the need to label
any ligands.”

With Saven and Liu providing a version of the receptor that could
stably bind to sheets of graphene, Johnson’s team refined the process
of manufacturing those sheets and connecting them to the circuitry
necessary to make functional devices.

The opioid receptor produces a change in the surrounding
graphene’s electrical properties whenever it binds to its target. This
change produces electrical signals that can be transmitted to a
computer via neighbouring electrodes.

The high reliability of the manufacturing process could enable
applications in both clinical diagnostics and further research.
“It’s not clear whether the receptors on the devices are as selective as
they are in the biological context,” said Saven. “By working with receptorfunctionalised
graphene devices, however, not only can we make better
diagnostic tools, but we can also potentially get a better understanding
of how the biomolecular system actually works in the body.”

“Graphene gives us an advantage,” added Johnson, “in that its
uniformity allows us to make 192 devices on a one-inch chip, all at the
same time. There are still a number of things we need to work out, but
this is definitely a pathway to making these devices in large quantities.”

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