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Mass Common Brigham researchers are shining a strong new gentle into the viral darkness with the event of Luminescence CAscade-based Sensor (LUCAS), a speedy, transportable, highly-sensitive diagnostic instrument for processing complicated organic samples.
In comparison with its diagnostic predecessors, LUCAS creates 500-fold stronger and eight-fold longer-lasting bioluminescence alerts, overcoming longstanding challenges confronted by point-of-care diagnostics. Their examine was revealed in Nature Biomedical Engineering.
“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. Finding an HIV particle in a human blood sample is like finding an ice cube in a jelly-filled Olympic swimming pool while blindfolded,” stated senior writer Hadi Shafiee, Ph.D., a school member within the Division of Engineering in Medication and Renal Division of Medication at Brigham and Ladies’s Hospital.
“With its novel enzyme cascade approach, LUCAS marks a substantial leap forward for sensing viruses in these complex biological samples.”
Level-of-care diagnostics have grow to be important instruments in lots of households, as folks measure their blood sugar, take being pregnant checks, and even conduct their very own COVID-19 assays. These diagnostics, which permit folks to forgo tedious, costly laboratory testing, are essential for illness detection, remedy, and monitoring.
But present diagnostics can fall quick, with faults like inaccuracy and poor sensitivity. Bioluminescence has the potential to alleviate frequent shortcomings skilled by different strategies, like background noise, false positives, photobleaching and phototoxicity.
Bioluminescence makes use of the identical pure enzyme that makes fireflies glow to gentle up organic samples for imaging. The enzyme, luciferase, is added to a pattern to search out and flag viral particles. Then, luciferin molecules are launched to that pattern, prompting a luciferase response that creates a burst of sunshine. However this response produces a light-weight sign that’s each weak and short-lived.
Shafiee and group developed a novel enzyme sign cascade to strengthen and delay bioluminescence alerts. They introduce one other enzyme to the equation, referred to as beta-galactosidase, that sticks to luciferin and releases it constantly, slightly than permitting luciferin to drift freely within the pattern for one-and-done reactions.
This additional step means extra luciferin, extra luciferase reactions, and extra bioluminescence. The truth is, this step enabled LUCAS to be 515 occasions extra bioluminescent than non-LUCAS methods, and LUCAS alerts maintained 96% power after an hour.
To guage LUCAS’ efficacy, the group used 177 viral-spiked affected person samples and 130 viral-spiked serum samples contaminated with both SARS-CoV-2, HIV, HBV, or HCV. SARS-CoV-2 affected person samples had been collected through nasopharyngeal swab, whereas HIV, HBV, and HCV samples had been collected through blood draw. LUCAS offered diagnostic solutions inside 23 minutes and with a mean accuracy throughout all pathogens of over 94%.
The researchers designed LUCAS to be each transportable and simple to make use of in order that it may be an possibility for high- and low-resource point-of-care environments. As a subsequent step, the group shall be testing LUCAS’ efficacy in different organic fluids and whether or not the tactic can determine multiple pathogen without delay.
Shafiee additionally notes that biomarker identification for a lot of illnesses, together with Alzheimer’s, is a quickly evolving area—so having a instrument like LUCAS able to go as new biomarkers emerge might show impactful in years to return.
“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,” stated first writer Sungwan Kim, Ph.D., a postdoctoral researcher in Shafiee’s lab at Brigham.
“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.”
Extra data:
Kim S, et al. Ultrasensitive and long-lasting bioluminescence immunoassay for point-of-care viral antigen detection, Nature Biomedical Engineering (2025). DOI: 10.1038/s41551-025-01405-9
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Diagnostic instrument creates stronger, longer-lasting bioluminescence alerts to detect viruses (2025, Might 30)
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