A groundbreaking advancement in the early detection of cancer biomarkers has emerged from a team of researchers led by Han Zhang at Shenzhen University, China. This innovative technology introduces a light-based sensor boasting extraordinary sensitivity, capable of identifying cancer biomarkers present at sub-attomolar concentrations in blood samples. Such sensitivity promises transformative impacts on medical diagnostics, enabling clinicians to detect the earliest signs of cancer and other diseases through a straightforward blood test, potentially long before conventional imaging techniques reveal abnormalities.
Cancer and a host of other diseases manifest on a molecular level through specific biomarkers, including proteins, nucleic acids such as DNA or RNA, and various other molecular entities. The challenge with these biomarkers lies in their infinitesimal concentrations during the disease’s nascent phase, often evading detection by existing diagnostic tools. Addressing this, the newly developed sensor harnesses a multi-disciplinary approach merging nanotechnology, gene editing, and nonlinear optics to amplify detection capabilities without relying on molecular amplification methods traditionally used in biomarker assays.
At the heart of this sensor is the phenomenon known as second harmonic generation (SHG), a nonlinear optical process wherein incident photons interacting with certain materials are effectively converted into photons of twice the energy — or half the wavelength. The sensor employs molybdenum disulfide (MoS₂), a two-dimensional semiconductor distinguished by its robust SHG response. By leveraging the MoS₂’s properties, the device creates a platform where subtle biochemical interactions translate directly into measurable optical signals, circumventing common issues with background noise that plague many light-based assays.
To precisely modulate the interaction distance essential for enhancing SHG signals, the team implemented DNA tetrahedrons as nanoscopic scaffolds. These tetrahedral structures are meticulously self-assembled from DNA strands, forming rigid, pyramid-like shapes with nanometer precision. Quantum dots, semiconductor nanoparticles renowned for their size-tunable optical characteristics, were tethered to these DNA frameworks. This arrangement enables fine control over the spatial orientation and proximity of quantum dots relative to the MoS₂ surface, thereby dramatically boosting the local electromagnetic field and, consequently, the SHG intensity.
The sensor’s biomarker specificity and detection mechanism owe much to the integration of CRISPR-Cas12a, a precise gene-editing protein programmed to identify target nucleic acid sequences indicative of disease biomarkers. Upon recognizing its target, Cas12a activates collateral cleavage activity, slicing the DNA strands anchoring the quantum dots. This cleavage disrupts the engineered nanostructure, precipitating a measurable decrease in SHG signal. The direct correlation between the presence of the biomarker and SHG signal modulation endows the sensor with remarkable sensitivity and specificity, enabling detection without the need for traditional amplification methods such as PCR.
This amplification-free detection is a profound leap forward, as conventional biomarker assays often entail time-consuming and costly amplification cycles to elevate the signal beyond detectable thresholds. By contrast, the current technology’s design — combining optical nonlinearity for noise suppression, nanometer-scale engineering for signal enhancement, and molecular precision via CRISPR — fosters rapid and accurate biomarker quantification directly from clinical samples. Such efficiency is poised to redefine the landscape of molecular diagnostics.
In practical application, the team focused on miR-21, a microRNA implicated as a lung cancer biomarker. Initial tests in buffer solutions established baseline sensitivity, followed by validation within human serum extracted from lung cancer patients. The sensor demonstrated exceptional performance, effectively distinguishing the target microRNA from a milieu of structurally similar RNA molecules present in serum, underscoring both its specificity and robustness. This real-world applicability suggests a viable path toward clinical translation.
Beyond lung cancer, the sensor’s modular design and programmable DNA constructs imply versatility across a plethora of diseases and biomarkers. The detection scheme could readily adapt to viruses, bacterial pathogens, and other disease-relevant molecules, unlocking potential applications in infectious disease surveillance, environmental monitoring, and neurodegenerative disease diagnostics, such as Alzheimer’s biomarkers. This universality underscores the sensor’s broad impact potential across multiple domains of healthcare and beyond.
Looking forward, the research team has ambitious plans to transform this laboratory-scale technology into a portable, user-friendly device. Miniaturizing the optical setup and integrating it into a compact form factor could enable bedside or point-of-care testing, expanding accessibility to underserved and remote locations lacking sophisticated laboratory infrastructure. Such advancements would democratize early disease detection, empowering timely interventions and personalized patient management.
The union of DNA nanotechnology, quantum dot-enhanced nonlinear optics, and CRISPR-based molecular recognition represents a triumph of interdisciplinary innovation. This synergy facilitates an elegant sensing architecture that balances speed, precision, and minimal complexity—characteristics critical for next-generation diagnostic tools. As the technology matures and moves toward commercialization, its capacity to reshape cancer diagnostics and monitoring stands to significantly impact patient outcomes and healthcare economics.
Published in the journal Optica, under the title “Sub-Attomolar-Level Biosensing of Cancer Biomarkers Using SHG Modulation in DNA Programmable Quantum Dots/MoS₂ Disordered Metasurfaces,” this research marks a seminal contribution to the field of biomedical optics. The detailed mechanisms and experimental validations outlined exemplify how fundamental physics and molecular biology can converge to create disruptive technologies in medicine.
In summary, the development of this highly sensitive SHG-based biosensor integrates the nanoprecision of DNA assembly, the optical enhancement of quantum dots, and the molecular specificity of CRISPR-Cas12a. This marriage of techniques enables the amplification-free detection of cancer biomarkers at previously unattainable sensitivity levels, bringing the prospect of rapid, accurate, and non-invasive cancer detection closer to reality. As such, it holds tremendous promise for revolutionizing how clinicians detect and monitor diseases, ultimately facilitating earlier interventions and improving survival outcomes worldwide.
Subject of Research: Cancer biomarker detection using light-based sensing technologies.
Article Title: Sub-Attomolar-Level Biosensing of Cancer Biomarkers Using SHG Modulation in DNA Programmable Quantum Dots/MoS₂ Disordered Metasurfaces
Web References:
DOI Link
Optica Journal Homepage
References:
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” Optica, 13 (2025).
Image Credits: Han Zhang, Shenzhen University
Keywords: Cancer research, Quantum dots, Metasurfaces, Clinical medicine
Tags: blood test for biomarkerscancer diagnostics technologyearly detection of cancergene editing in cancer researchinnovative cancer biomarkerslight-based cancer detectionnanotechnology in diagnosticsnonlinear optics applicationssecond harmonic generation in sensorsShenzhen University cancer researchsub-attomolar concentration detectiontransformative medical diagnostics
