Biomarkers, including proteins and DNA fragments, can indicate the presence of cancer, its progression, and a person's likelihood of developing the disease. However, these markers are often found in very low concentrations during the initial stages, making detection challenging with traditional methods.
According to Han Zhang, the leader of the research team from Shenzhen University in China, "Our sensor merges DNA-based nanostructures with quantum dots and CRISPR gene editing technology to identify subtle biomarker signals through a light-based technique called second harmonic generation (SHG)." He added that if successful, this innovation could simplify treatment processes, enhance survival rates, and reduce healthcare costs.
In the journal Optica, the team reported their device's capability to detect lung cancer biomarkers in patient samples at sub-attomolar concentrations. Even with minimal molecules present, the system generated a clear and quantifiable signal. This adaptable platform could also potentially identify viruses, bacteria, environmental toxins, or biomarkers related to conditions like Alzheimer's disease.
Zhang emphasized, "This technique shows great potential for facilitating straightforward blood tests for lung cancer before tumors become visible on CT scans. It may also support personalized treatment by enabling doctors to track a patient's biomarker levels frequently, rather than waiting for lengthy imaging results."
Innovative Optical Sensing Technology
Current biomarker testing methods often necessitate chemical amplification to enhance minute molecular signals, adding time and complexity. The researchers sought to develop a direct detection strategy that bypasses these additional procedures.
The system utilizes SHG, a nonlinear optical effect where incoming light transforms into light with half its wavelength. In this setup, SHG occurs on the surface of a two-dimensional semiconductor known as molybdenum disulfide (MoS₂).
To accurately position the sensing elements, the team constructed DNA tetrahedrons--small, pyramid-shaped nanostructures made entirely from DNA. These structures strategically hold quantum dots at specific distances from the MoS₂ surface, enhancing the local optical field and amplifying the SHG signal.
CRISPR-Cas gene editing technology was integrated to identify specific biomarkers. When the Cas12a protein recognizes its target, it cleaves the DNA strands anchoring the quantum dots, resulting in a measurable decrease in the SHG signal. The low background noise produced by SHG allows for the detection of extremely low biomarker concentrations with remarkable sensitivity.
Zhang noted, "We view DNA not just as a biological material but as programmable building blocks, enabling us to construct our sensor components with nanometer-level accuracy. Our method, combining optical nonlinear sensing with an amplification-free design, strikes a unique balance between speed and precision."
Successful Testing of Lung Cancer Biomarkers
To assess real-world applicability, the researchers focused on miR-21, a microRNA biomarker linked to lung cancer. After confirming the device's ability to detect miR-21 in a controlled buffer solution, they proceeded to test it using human serum from lung cancer patients, simulating an actual blood test.
Zhang remarked, "The sensor performed exceptionally well, demonstrating that the integration of optics, nanomaterials, and biology can create an effective device. It was also highly specific, targeting only the lung cancer biomarker while disregarding similar RNA strands."
The next step is to miniaturize the optical system, with researchers aiming to create a portable version suitable for bedside use, outpatient clinics, or remote areas with limited medical facilities.
