Scientists have created an ultra-sensitive blood test that can detect tiny traces of cancer-related molecules – at levels so low they are almost unimaginable.
The new test looks for microRNAs, very small pieces of genetic material that cancer cells release into the blood. Certain microRNAs, such as miRNA-21, miRNA-155, and miRNA-10b, are known to be linked to early tumor development. Because these molecules can appear in blood before a tumor is large enough to see on a scan, they are considered promising early warning signs of cancer.
The challenge for liquid biopsies is that these molecules exist in extremely tiny amounts – far smaller than most current tests can reliably detect. In this study, published in Optica, researchers developed a new optical sensing system that can measure microRNAs at “sub-attomolar” levels, with a reported detection limit of 168 zeptomolar. That means it can detect concentrations billions of times lower than many standard laboratory methods.
The technology combines several advanced tools. First, it uses light signals known as second-harmonic generation (SHG), which are very sensitive to small changes on a surface. The researchers built a layered structure using a single-atom-thick material called MoS₂ and tiny light-emitting particles known as quantum dots. These particles are positioned with nanometer precision using DNA “origami,” a technique that folds DNA into tiny shapes to act as scaffolds.
When a target cancer microRNA is present, a CRISPR-based molecular system cuts specific DNA linkers in the structure. This change alters the light signal, creating a clear and measurable drop in SHG intensity. Even extremely low concentrations produce a detectable signal change.
The system was tested using blood samples from lung cancer patients and healthy individuals. It showed stronger signal differences between groups than standard RT-qPCR testing.
Lead researcher Han Zhang said, "For early diagnosis, this method holds promise for enabling simple blood screenings for lung cancer before a tumor might be visible on a CT scan."
"It could also help advance personalized treatment options by allowing doctors to monitor a patient's biomarker levels daily or weekly to assess drug efficacy, rather than waiting months for imaging results," Zhang added.
