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Inhale nanoparticles then pee on a stick

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Inhale nanoparticles then pee on a stick

MIT scientists have developed an easier method for diagnosing lung cancer – breathe in some inhalable nanoparticle sensors, then pee on a stick.

Lung cancer is usually diagnosed through a CT scan, but it’s uncomfortable and has a high false-positive rate. Plus, the machines are big and expensive, so they aren’t available in all hospitals or healthcare facilities, especially in low income regions. But a new diagnostic tool from a team at MIT may make things simpler. Patients would just need to inhale some nanoparticles from a nebulizer, or even just a small device like an asthma inhaler, then pee on a paper test strip like a pregnancy test.

There’s an intriguing mechanism behind how it all works. The nanoparticles contain DNA “barcodes” that are designed to interact with certain enzymes, called proteases, which are overactive in tumors. If these proteases are present in a patient’s lungs, they’ll snip off a bit of the DNA barcode, which then winds up in the urine. The paper test strip can then detect these loose barcodes, returning a positive result for lung cancer.

The researchers tested the technique in mice that had been genetically engineered to develop human-like lung cancer. About 7.5 weeks after the tumors started to form, which correlated to stage 1 or 2 cancer in humans, the researchers administered the diagnostic test.

In the first experiments, the team was searching for 20 different biomarkers, but after using algorithms to identify the best combination, they narrowed it down to just four. This more manageable combo is what the test strips are searching for.

The researchers have been developing urine tests for cancer using this mechanism for a few years now, but this new work adds a few improvements. For one, previous versions required the nanoparticles to be injected into the bloodstream, but an inhalable version is less invasive and easier to store and administer around the world.

The other main advantage comes at the other end of the process. Previously, mass spectrometry was used to analyze the urine samples to find the DNA barcodes, but that requires bulky equipment that’s not always available. This time, they developed a lateral flow assay to detect the biomarkers – the same basic technology behind cheap, common pregnancy or COVID-19 tests.

“We were really pushing this assay to be point-of-care available in a low-resource setting, so the idea was to not do any sample processing, not do any amplification, just to be able to put the sample right on the paper and read it out in 20 minutes,” said Sangeeta Bhatia, senior author of the study. “The idea would be you come in and then you get an answer about whether you need a follow-up test or not, and we could get patients who have early lesions into the system so that they could get curative surgery or lifesaving medicines.”

In the lead-up to that, the team now plans to test the sensor panels with human biopsy samples to check how well it can detect human cancers, before eventually conducting clinical trials.

The research was published in the journal Science Advances.

Source: MIT

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