Biomarkers such as proteins, fragments of DNA, and other molecules can signal whether cancer is present, how it is progressing, or a person’s risk of developing it. The difficulty is that in the earliest stages of disease, these markers exist in extremely low concentrations, making them hard to measure with conventional tools.

“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 his team reported that the device detected lung cancer biomarkers in patient samples at sub-attomolar levels. Even when only a few molecules were present, the system produced a clear and measurable signal. Because the platform is programmable, it could potentially be adapted to identify viruses, bacteria, environmental toxins, or biomarkers linked to conditions such as 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.”

Amplification Free Optical Sensing Technology

Most current biomarker tests require chemical amplification to increase tiny molecular signals, which adds time, complexity, and expense. The researchers aimed to create a direct detection strategy that eliminates those additional steps.

The system relies on SHG, a nonlinear optical phenomenon in which incoming light is converted into light with half the wavelength. In this design, SHG takes place on the surface of a two dimensional semiconductor called molybdenum disulfide (MoS₂).

To precisely position the sensing components, the team built DNA tetrahedrons, which are small pyramid shaped nanostructures formed entirely from DNA. These structures hold quantum dots at carefully controlled distances from the MoS₂ surface. The quantum dots intensify the local optical field and boost the SHG signal.

CRISPR-Cas gene editing technology was then incorporated to recognize specific biomarkers. When the Cas12a protein detects its target, it cuts the DNA strands that anchor the quantum dots. This action triggers a measurable drop in the SHG signal. Because SHG produces very little background noise, the system can detect extremely low biomarker concentrations with high sensitivity.

“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.”

Successful Lung Cancer Testing in Human Serum

To evaluate real world performance, the researchers focused on miR-21, a microRNA biomarker associated with lung cancer. After confirming that the device could detect miR-21 in a controlled buffer solution, they tested it using human serum from lung cancer patients to simulate an actual 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.”

The next goal is to shrink the optical system. The researchers aim to develop a portable version that could be used at the bedside, in outpatient clinics, or in remote areas with limited medical resources.