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Diagnostic SHERLOCK now detects multiple diseases
February 24, 2018, 2:07 pm

The team that first unveiled the rapid, inexpensive, highly sensitive diagnostic tool called SHERLOCK (Specific High Sensitivity Reporter unLOCKing) have greatly enhanced the tool's power and application by developing a miniature paper test that allows results to be seen with the naked eye, without the need for any expensive equipment.

The SHERLOCK team, based at the Massachusetts Institute of Technology (MIT) and at Broad Institute of MIT and Harvard, have developed a simple paper strip to display test results for a single genetic signature, borrowing from the visual cues common in pregnancy tests. After dipping the paper strip into a processed sample, a line appears, indicating whether the target molecule was detected or not.

The team also increased the sensitivity of SHERLOCK and added the capacity to accurately quantify the amount of target in a sample and test for multiple targets at once. All together, these advancements accelerate SHERLOCK's ability to quickly and precisely detect genetic signatures, including pathogens and tumor DNA, in samples. The new advancement paves the way for field use, such as during an outbreak, and could potentially transform global research and public health.

The researcher team used SHERLOCK's modified capabilities to detect cell-free tumor DNA in blood samples from lung cancer patients and to detect synthetic Zika and Dengue virus simultaneously, in addition to other demonstrations.

The team envisions a wide range of uses for SHERLOCK, thanks to its versatility in nucleic acid target detection, including diagnosing infections in patients and detecting mutations that confer drug resistance or cause cancer, but it can also be used for industrial and agricultural applications where monitoring steps along the supply chain can reduce waste and improve safety.

SHERLOCK could initially only detect one nucleic acid sequence at a time, but now one analysis can give fluorescent signals for up to four different targets at once. For example, the new version of SHERLOCK can determine in a single reaction whether a sample contains Zika or dengue virus particles, which both cause similar symptoms in patients. The platform uses different enzymes from different species of bacteria to generate the additional signals.

SHERLOCK's second iteration also uses an additional enzyme to amplify its detection signal, making the tool more sensitive than its predecessor. With the original SHERLOCK, researchers were detecting a single molecule in a microliter, but now they can achieve 100-fold greater sensitivity. "That's especially important for applications like detecting cell-free tumor DNA in blood samples, where the concentration of your target might be extremely low. This next generation of features helps make SHERLOCK a more precise system," said the team.


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