While anesthesiologists are confidently knocking people out and waking them up on a daily basis, giving them analgesics and related meds, a lot of the mechanisms of the drugs they use are poorly understood. To help in uncovering how opioids operate, researchers at University of Pennsylvania developed a completely electronic μ-opioid sensor that can be used as a laboratory instrument.
The investigators developed an artificial μ-opioid receptor protein that was modified to be soluble in water in order to make it practical for lab work. It was then bound to a graphene substrate that acted as a field-effect transistor capable of detecting its electric properties when the μ-opioid receptor is activated. The team was able to fit about 200 of such devices on a single square inch chip, of which only one failed during testing.
“We can measure each device individually and average the results, which greatly reduces the noise,” A.T. Charlie Johnson, director of Penn’s Nano/Bio Interface Center and professor of physics in Penn Arts & Sciences, says. “Or you could imagine attaching 10 different kinds of receptors to 20 devices each, all on the same chip, if you wanted to test for multiple chemicals at once.”
In the researcher’s experiment, they tested their devices’ ability to detect the concentration of naltrexone, a drug used in alcohol and opioid addiction treatment because it binds to—and blocks—the natural opioid receptors that produce the narcotic effects patients seek.
“It’s not clear whether the receptors on the devices are as selective as they are in the biological context,” Jeffery Saven, professor of chemistry in Penn Arts & Sciences, says, “as the ones on your cells that can tell the difference between an agonist, like morphine, and an antagonist, like naltrexone, which binds to the receptor but does nothing. By working with the receptor-functionalized graphene devices, however, not only can we make better diagnostic tools, but we can also potentially get a better understanding of how the bimolecular system actually works in the body.”
Liu notes that many novel opioids have been developed over the centuries, however, none of them has achieved potent analgesic effects without notorious side effects, including devastating addiction and respiratory depression.
“This novel tool could potentially aid the development of new opioids that minimize these side effects,” he says.
Study in Nano Letters: Scalable Production of Highly Sensitive Nanosensors Based on Graphene Functionalized with a Designed G Protein-Coupled Receptor…
UPenn: A cyborg sensor that could unlock anesthesia’s secrets…