Researchers at Shenzhen University in China have developed a highly sensitive, light-based sensor capable of detecting extremely low concentrations of cancer biomarkers in blood samples, potentially enabling diagnosis long before tumors are visible on traditional scans. The technology, detailed in the journal Optica, utilizes a novel combination of DNA nanotechnology, CRISPR gene editing, and quantum dots to amplify faint biomarker signals.
The core challenge in optical biosensing, according to the Shenzhen team, lies in detecting biomolecules at ultralow concentrations due to the weak interactions between light and matter. Their approach leverages nonlinear optics, specifically second harmonic generation (SHG), to enhance these faint optical responses. SHG is an optical process where light interacting with certain materials doubles in frequency, effectively amplifying the signal.
The sensor’s architecture is bioinspired, employing DNA tetrahedrons – pyramid-shaped nanostructures assembled from DNA – to precisely position quantum dots near a molybdenum disulfide surface. These quantum dots, made from cadmium telluride and zinc sulfide (CdTe/ZnS), enhance the local optical field when illuminated, strengthening the SHG signal when a biomarker molecule is present. “Our sensor combines nanostructures made of DNA with quantum dots and CRISPR gene editing technology to detect faint biomarker signals using second harmonic generation,” explained Han Zhang, the research team leader from Shenzhen University.
The CRISPR component of the sensor acts as a highly specific switch. The Cas12a protein, a key enzyme in the CRISPR system, is programmed to recognize a specific biomarker. When the target biomarker is detected, Cas12a cuts the DNA structures holding the quantum dots in place, reducing the SHG signal and providing a clear indication of the biomarker’s presence. This dual-signal approach – amplification through SHG and reduction upon biomarker detection – enhances both sensitivity and accuracy.
In initial trials, the sensor was used to detect miR-21, a microRNA biomarker associated with lung cancer. Results demonstrated a 124-fold boost in SHG signals. Crucially, the sensor achieved “unprecedented detection limits of 168 zM for microRNAs, representing an improvement of over six orders of magnitude compared to conventional optical biosensors,” the researchers reported. The sensor also exhibited high specificity, accurately identifying the lung cancer biomarker without reacting to similar RNA strands.
Researchers are now focused on miniaturizing the optical setup to create a portable device suitable for use at the point of care – in clinics, at the bedside, or even in remote locations with limited resources. “By combining optical nonlinear sensing, which effectively minimizes background noise, with an amplification-free design, our method offers a distinct balance of speed and precision,” Zhang stated. “If successful, this approach could help make disease treatments simpler, potentially improve survival rates and lower overall healthcare costs.”
