WASHINGTON — Researchers have developed a highly sensitive light-based sensor that can detect extremely low concentrations of cancer biomarkers in the blood. The new technology could one day make it possible to spot early signs of cancer and other conditions using a simple blood test.
Biomarkers such as proteins, DNA or other molecules can be used to reveal the presence, progression or risk of cancer and other diseases. However, one of the main challenges in early disease diagnosis is the extremely low concentration of biomarkers present at the onset.
"Our sensor combines nanostructures made of DNA with quantum dots and CRISPR gene editing technology to detect faint biomarker signals using a light-based approach known as second harmonic generation (SHG)," said research team leader Han Zhang from Shenzhen University in China. "If successful, this approach could help make disease treatments simpler, potentially improve survival rates and lower overall healthcare costs."
In Optica , Optica Publishing Group 's journal for high-impact research, Zhang and colleagues show that their sensor can detect lung cancer biomarkers from patient samples at sub-attomolar levels, producing a clear signal even when only a few molecules were present in a sample. The sensing technique was designed to be programmable, which could allow it to detect viruses, bacteria or environmental toxins as well as various biomarkers such as those associated with Alzheimer's disease.
"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," said Zhang. "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."
Detection without amplification
Detecting biomarkers usually requires amplifying tiny amounts of molecules, a process that can be time-consuming and costly. In the new work, the researchers wanted to develop a direct sensing approach that could identify low-concentration biomarkers without complex amplification steps.
The new sensor is based on SHG, a nonlinear optical process in which incoming light is converted to light at half the wavelength. In this case, SHG occurs at the surface of the two-dimensional semiconducting material molybdenum disulfide (MoS₂).
The researchers used DNA tetrahedrons — self-assembled, pyramid-like nanostructures made entirely from DNA — to tether tiny quantum dots at precise distances from the MoS₂ surface. The quantum dots enhance the local optical field, strengthening the SHG signal.
They then applied CRISPR-Cas gene editing to detect specific biomarkers. When the Cas12a protein used for CRISPR recognizes a target biomarker, it cuts the DNA holding the quantum dots in place, which causes a measurable drop in SHG signal. Because the SHG signal has minimal background noise, even very low concentrations of biomarkers can be detected.
"Instead of viewing DNA only as a biological substance, we use it as programmable building blocks, allowing us to assemble the components of our sensor with nanometer-level precision," said Zhang. "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."
Testing with clinical samples
The researchers tested the sensor by using it to detect miR-21, a microRNA biomarker associated with lung cancer. After verifying that it could detect this marker in a simple buffer solution, they also showed that it could detect the biomarker in human serum from lung cancer patients, simulating a real blood test.
"The sensor worked exceptionally well, showing that integrating optics, nanomaterials and biology can be an effective strategy to optimize a device," said Zhang. "The sensor was also highly specific — ignoring other similar RNA strands and detecting only the lung cancer target."
Next, the researchers plan to focus on miniaturizing the optical setup. Their goal is to turn it into a portable device that could be used at the bedside, in clinics or even in low-resource remote locations.
Paper: B. Du, X. Tian, S. Han, Y. Liu, Z. Chen, Y. Liu, L. Li, Z. Xie, L. Gao, K. Jiang, Q. Jiang, S. Chen, H. Zhang, "Sub-Attomolar-Level Biosensing of Cancer Biomarkers Using SHG Modulation in DNA Programmable Quantum Dots/MoS2 Disordered Metasurfaces" 13, (2025).
DOI: 10.1364/OPTICA.577416 .
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