Researchers at Shenzhen University have developed a light-based biosensor capable of detecting ultra-low concentrations of cancer biomarkers in blood, potentially enabling earlier diagnosis through minimally invasive screening.
The work, published in Optica, demonstrates detection of lung cancer–associated microRNA at sub-attomolar concentrations, levels corresponding to only a few molecules in a sample.
The system integrates DNA nanostructures, quantum dots and CRISPR-based molecular recognition within an optical sensing framework designed to operate without biochemical amplification.
Direct detection without molecular amplification
Early-stage disease diagnostics are often constrained by the extremely low abundance of biomarkers, including circulating DNA, RNA or protein fragments.
Conventional detection approaches typically rely on amplification processes, which can increase complexity, time and cost.
The newly reported sensor uses a nonlinear optical phenomenon known as second harmonic generation (SHG), in which incident light is converted into light at half its wavelength.
In this system, SHG occurs at the surface of molybdenum disulfide (MoS₂), a two-dimensional semiconducting material.
DNA tetrahedrons, self-assembled nanostructures composed entirely of DNA, are used as programmable scaffolds to position quantum dots at controlled distances from the MoS₂ surface.
The quantum dots enhance the local electromagnetic field, amplifying the SHG response without requiring molecular target amplification.
When the CRISPR-associated protein Cas12a recognizes a target biomarker sequence, it cleaves the DNA tether anchoring the quantum dots. This structural change reduces the SHG signal, generating a measurable optical readout.
According to research team leader Han Zhang, the combination of nonlinear optics and amplification-free detection enables high sensitivity with minimal background noise.
Clinical validation in lung cancer samples
The team validated the platform using miR-21, a microRNA biomarker associated with lung cancer. Following detection in controlled buffer solutions, the researchers demonstrated successful identification of miR-21 in human serum samples from lung cancer patients.
The system was reported to exhibit high specificity, distinguishing the target RNA sequence from closely related strands.
Because the sensing architecture is programmable, the platform could be adapted to detect additional disease biomarkers, including those associated with neurodegenerative disorders, viral infections or bacterial pathogens.
Future development will focus on miniaturizing the optical hardware to enable deployment in clinical and point-of-care settings. The researchers aim to integrate the sensing components into a portable format suitable for bedside diagnostics or use in resource-limited environments.
If translated into clinical practice, the platform could support earlier detection of cancers prior to imaging-visible tumor formation and enable more frequent monitoring of biomarker levels during treatment.
By combining nanomaterials engineering, programmable DNA structures and CRISPR-based molecular recognition within a low-noise optical detection system, the study outlines a potential pathway toward scalable, high-sensitivity blood diagnostics without reliance on conventional amplification techniques.
