The diagnostic, which requires only a simple urine test to read the results, could make lung cancer screening more accessible worldwide.

Using a new technology developed at MIT, diagnosing lung cancer could become as easy as inhaling nanoparticle sensors and then taking a urine test that reveals whether a tumor is present.

The new diagnostic is based on nanosensors that can be delivered by an inhaler or a nebulizer. If the sensors encounter cancer-linked proteins in the lungs, they produce a signal that accumulates in the urine, where it can be detected with a simple paper test strip.

This approach could potentially replace or supplement the current gold standard for diagnosing lung cancer, low-dose computed tomography (CT). It could have an especially significant impact in low- and middle-income countries that don’t have widespread availability of CT scanners, the researchers say.

“Around the world, cancer is going to become more and more prevalent in low- and middle-income countries. The epidemiology of lung cancer globally is that it’s driven by pollution and smoking, so we know that those are settings where accessibility to this kind of technology could have a big impact,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science.

To help diagnose lung cancer as early as possible, the U.S. Preventive Services Task Force recommends that heavy smokers over the age of 50 undergo annual CT scans. However, not everyone in this target group receives these scans, and the high false-positive rate of the scans can lead to unnecessary, invasive tests.

Bhatia has spent the last decade developing nanosensors for use in diagnosing cancer and other diseases, and in this study, she and her colleagues explored the possibility of using them as a more accessible alternative to CT screening for lung cancer.

These sensors consist of polymer nanoparticles coated with a reporter, such as a DNA barcode, that is cleaved from the particle when the sensor encounters enzymes called proteases, which are often overactive in tumors. Those reporters eventually accumulate in the urine and are excreted from the body.

Previous versions of the sensors, which targeted other cancer sites such as the liver and ovaries, were designed to be given intravenously. For lung cancer diagnosis, the researchers wanted to create a version that could be inhaled, which could make it easier to deploy in lower resource settings.

The researchers tested their diagnostic system in mice that are genetically engineered to develop lung tumors similar to those seen in humans. The sensors were administered 7.5 weeks after the tumors started to form, a time point that would likely correlate with stage 1 or 2 cancer in humans.

In their first set of experiments in the mice, the researchers measured the levels of 20 different sensors designed to detect different proteases. Using a machine learning algorithm to analyze those results, the researchers identified a combination of just four sensors that was predicted to give accurate diagnostic results. They then tested that combination in the mouse model and found that it could accurately detect early-stage lung tumors.

For use in humans, it’s possible that more sensors might be needed to make an accurate diagnosis, but that could be achieved by using multiple paper strips, each of which detects four different DNA barcodes, the researchers say.