In the days following a lung transplant, a condition known as primary graft dysfunction can prevent the organ from properly taking in and circulating oxygen. The disorder afflicts 10 to 25% of patients, studies estimate. It proves lethal nearly half the time.
Researchers have now developed sensors that rapidly screen donor lungs for molecular warning signs of this disorder before the organs reach patients (Sci. Adv. 2015, DOI: 10.1126/sciadv.1500417).
Although surgeons already have methods to examine donor lungs for biomarkers linked to primary graft dysfunction, these techniques require several hours to report results—more time than transplant surgeons typically have. The new sensors can provide results in less than 20 minutes, says Shana O. Kelley, who led the research team along with lung transplant specialist Shaf Keshavjee and graduate researcher Andrew T. Sage at the University of Toronto.
This rapid testing relies on synthetic chains of nucleic acids, which are attached to spiky gold electrodes on glass chips. The team chose a set of these synthetic probes that selectively bind to three messenger RNA molecules associated with primary graft dysfunction. Researchers don’t fully understand how this trio contributes to the disorder, but two are tied to tissue inflammation, Kelley says.
When a probe molecule binds to its partner mRNA molecule, the gold electrodes record an electron flux that signals the interaction, enabling the researchers to quantify the biomarkers present in the donor tissue.
By sampling 52 human donor lungs selected for transplantation, the team demonstrated that their sensors could predict primary graft dysfunction.
Such devices could help get lungs to more patients who need them, says Jason D. Christie, director of the Center for Translational Lung Biology at the University of Pennsylvania. “A lot of people die on the lung transplant wait list,” Christie says. Surgeons lack rapid, reliable, quantitative tools to analyze donor lungs and won’t transplant organs that appear suspect, he says. But many of these organs are actually suitable transplants.
Kelley hopes her team’s research will help rescue serviceable lungs. “This is exciting,” she says. “It’s been fascinating to see how new sensor chemistry can create a solution to this problem.”