Selectivity and stability reshaping high-sensitivity detection boundaries: A technical leap and paradigm shift in semiconductor surface-enhanced Raman scattering
image: This schematic illustrates the four core enhancement strategies—energy level customization, amorphization, quasi-metallization, and morphology control—that underpin the recent leap in semiconductor-based surface-enhanced Raman scattering (SERS). These rationally designed material approaches modulate electronic band structures and charge transfer processes, achieving high sensitivity, selectivity, and stability. The resulting substrates are being applied in transformative fields such as virus detection (e.g., SARS-CoV-2 identification), food safety monitoring (e.g., trace bisphenol A), cancer diagnosis (e.g., early lung cancer biomarker detection), and volatile organic compound sensing, paving the way for next-generation analytical platforms in healthcare, environment, and security.
Credit: Nano Research, Tsinghua University Press
Marking the 50th anniversary of the discovery of surface-enhanced Raman scattering (SERS), a multidisciplinary team of Chinese researchers has published a comprehensive Perspective in Nano Research, charting a transformative leap toward rationally designed semiconductor substrates for ultrasensitive, molecule-selective detection. The article, published online on December 14, 2025, systematically outlines how advanced material engineering strategies are reshaping the sensitivity, selectivity, and stability of SERS technology, paving the way for its deployment in next-generation biosensing and clinical diagnostics.
The team, led by corresponding author Bing Zhao from Jilin University and involving collaborators from Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences,, Shanghai Institute of Ceramics, Beihang University, and over ten other institutions, details four core enhancement strategies that underpin this paradigm shift. These include energy-level customization through defect and alloy engineering, amorphization to create abundant charge-transfer channels, quasi-metallization of materials like transition metal nitrides for synergistic enhancement, and morphology control to harness effects like Mie resonance and molecular enrichment.
“Our work summarizes the concerted efforts across the community to move beyond traditional metal-based SERS,” said Bing Zhao. “By rationally designing the electronic structure and surface properties of semiconductors, we can now achieve not only remarkable enhancement factors but also intrinsic selectivity toward specific target molecules, which is crucial for real-world applications.”
The review highlights groundbreaking applications enabled by these advances. For instance, semiconductor SERS substrates have achieved femtomolar-level sensitivity, allowing for the identification of non-infectious SARS-CoV-2 virus particles—a capability that addresses limitations of standard PCR tests. In cancer diagnostics, platforms such as Cu-doped SnO₂-NiO heterojunctions can detect early-stage lung cancer biomarkers at parts-per-billion levels. Furthermore, novel materials like single-atom-copper-anchored metal-organic frameworks (MOFs) enable rapid, on-site detection of volatile organic compounds within minutes.
Despite the rapid progress, the authors identify a critical bottleneck: the lack of standardized protocols for substrate fabrication, performance quantification, and data comparison. They note that international bodies like ISO and ASTM have begun addressing these gaps, but widespread adoption demands continued multi-stakeholder collaboration.
The researchers envision semiconductor SERS evolving into a core analytical platform for precision medicine, food safety, and public health surveillance. They emphasize that interdisciplinary cooperation among chemists, physicists, engineers, and clinicians will be key to translating these sensitive, selective, and stable sensing systems from the laboratory into daily practice.
Other contributing authors include Jie Lin, Xiangyu Meng, Yujiao Xie, Yusi Peng, Kun Liang, Fugang Xu, Aiguo Shen, Libin Yang, Lei Chen, Wei Ji, Tingting Zheng, Teng Qiu, Shan Cong, Zhigang Zhao, Xiaotian Wang, Yong Yang, Aiguo Wu, and Guangcheng Xi from institutions across China.
This work was supported by the National Natural Science Foundation of China (Grants No. 12374390, 12274018, 52473250, 52501244).
DOI Link:
https://doi.org/10.26599/NR.2026.94908347
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.