Animals that produce their own light source, through an internal chemical reaction, are one of the many wonders of nature – and something biotechnology scientists have been working hard to replicate and adapt for human use for some time.
Now, researchers at Mass General Brigham have made a breakthrough by mixing up the recipe for that chemical reaction, creating a bioluminescence diagnostic tool that's 515 times brighter and eight times more enduring than current models. It isn't just brighter, but retains most of its glow – 96% of it – after an hour, which leapfrogs the hurdles faced by existing tools.
Called Luminescence CAscade-based Sensor (LUCAS), this tool uses the natural "ingredients" in the production of bioluminescence – the light-emitting molecule luciferin, which reacts with the enzyme luciferase. Traditionally, replicating nature's glow has worked, to a point. Scientists have been able to produce this reaction but have been unable to sustain the glow for long. LUCAS, however, also features an enzyme known as beta-galactosidase, which attaches to luciferin and regulates the release of its light-emitting properties.
As such, the tool is not just significantly stronger but enduring, allowing for an efficient way to detect and light up hard-to-find virus particles with a single reaction.
“Developing effective diagnostics is incredibly challenging, especially when you think about the size of infectious disease particles and the complicated biological fluids we’re attempting to identify them in,” said senior author Hadi Shafieee, a researcher at Brigham and Women's Hospital. “Finding an HIV particle in a human blood sample is like finding an ice cube in a jelly-filled Olympic swimming pool while blindfolded. With its novel enzyme cascade approach, LUCAS marks a substantial leap forward for sensing viruses in these complex biological samples.”
The researchers tested the new tool against 177 viral-spiked patient samples and 130 viral-spiked serum samples infected with a range of pathogens – SARS-CoV-2, HIV, HBV, or HCV. Samples of what we know as COVID-19 were gathered via nasal swab, while the others through bloodwork. Incredibly, LUCAS was able to help scientists determine the virus within 23 minutes, and had an accuracy rate that averaged more than 94% across all infections.
Buoyed by the breakthrough, the researchers will now enlist LUCAS to detect pathogens in other biological fluids, as well as test whether it can identify multiple viruses in a single sample. And the team says the tool – which is designed to be portable and easy to use – could be adapted to identify other disease biomarkers, such as the ones we know of for Alzheimer's.
“We always want to detect infection and disease as early as possible, as that can make all the difference when it comes to care and long-term outcomes,” said first author Sungwan Kim, a postdoctoral researcher in Shafiee’s lab. “With our focus on developing diagnostic tools that are sensitive, accurate, and accessible, we want to make early detection easier than it has ever been and push personalized care into a new era.”
The study was published in the journal Nature Biomedical Engineering.
Source: Mass General Brigham
