A new CRISPR-powered light sensor can detect the faintest whispers of cancer in a single drop of blood.
Scientists have created an advanced light-based sensor capable of identifying extremely small amounts of cancer biomarkers in blood. The technology could eventually allow doctors to detect early warning signs of cancer and other diseases through a routine blood test.
Biomarkers such as proteins, fragments of DNA, or other molecules can signal whether cancer is present, how it is progressing, or a person's level of risk. The challenge is that at the earliest stages of disease, these molecules exist in very tiny amounts, making them difficult to measure.
"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."
Writing in Optica, Optica Publishing Group's journal for high-impact research, Zhang and colleagues reported that the sensor detected lung cancer biomarkers in patient samples at sub-attomolar levels. That means it was able to generate a clear signal even when only a handful of molecules were present. Because the system 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 methods for detecting biomarkers require chemical amplification to boost tiny molecular signals, a process that can add time, complexity, and cost. The researchers aimed to design a direct detection method that avoids these extra steps.
The new platform relies on SHG, a nonlinear optical effect in which incoming light is transformed into light with half the wavelength. In this system, SHG takes place on the surface of a two-dimensional semiconductor called molybdenum disulfide (MoS2).
To fine-tune the signal, the team used DNA tetrahedrons, which are small pyramid-shaped nanostructures built entirely from DNA, to position quantum dots at exact distances from the MoS2 surface. These quantum dots intensify the local optical field, strengthening the SHG response.
CRISPR-Cas gene editing was then incorporated to recognize specific biomarkers. When the Cas12a protein identifies its target, it cuts the DNA strands anchoring the quantum dots. This action produces a measurable decrease in the SHG signal. Because the SHG technique generates 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 Tests With Lung Cancer Samples
To evaluate performance, the researchers focused on miR-21, a microRNA linked to lung cancer. After confirming detection in a controlled buffer solution, they tested the sensor using human serum from lung cancer patients, mimicking real-world blood testing conditions.
"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 step is to shrink the optical system. The team hopes to develop a compact, portable device suitable for bedside use, outpatient clinics, or remote areas with limited medical resources.
Reference: "Sub-Attomolar-Level Biosensing of Cancer Biomarkers Using SHG Modulation in DNA-Programmable Quantum Dots/MoS2 Disordered Metasurfaces" by Siyi Han, lingfeng gao, Qiao Jiang, Wenbo Du, Shi Chen, Yi Liu, Han Zhang, Xilin Tian, Yong Liu, Zheng Xie, Linjun Li, Ke Jiang and Zhi Chen, 12 February 2026, Optica.
DOI: 10.1364/OPTICA.577416
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