image: TiO₂ probe: amorphous, hollow structure with a size of approximately 150 nm, suitable for loading Raman reporter molecules (e.g., crystal violet, CV). IO probe: highly crystalline, with a size of approximately 10 nm, exhibiting good magnetic responsiveness for magnetic enrichment.
Credit: Yujiao Xie, Aiguo Wu, Jie Lin, et al.
The detection of circulating tumor cells (CTCs) has great clinical value for early cancer diagnosis and the identification of metastatic spread. However, due to the extreme rarity of CTCs and the high background of leukocytes, achieving efficient and accurate detection remains a major challenge.
In a study published in the KeAi journal Nano Biomedicine and Engineering, researchers from the Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, and its affiliated Ningbo Cixi Institute of Biomedical Engineering, have introduced a novel ratiometric SERS platform based on dual functionalized bioprobes (TiO₂-CV-rBSA-FA and IO-AR-PDA-EpCAM).
"This platform effectively eliminates environmental interference through signal self-calibration," says co-corresponding author Yujiao Xie. "It achieved a limit of detection (LOD) as low as 5 × 10⁻⁷ M, a relative standard deviation (RSD) of less than 10%, and cell viability exceeding 90%, offering a new strategy for highly sensitive and stable detection of rare CTCs in liquid biopsy."
The platform utilizes the intensity ratio between the internal reference signal and the response signal for self-calibration, effectively eliminating environmental interference and significantly enhancing detection stability.
"This system consists of dual bioprobes: a magnetic iron oxide nanoparticle (IO NP) modified with acridine red and an EpCAM antibody (IO-AR-PDA-EpCAM), which provides an internal reference SERS signal using Alizarin Red (AR) and enables target capture; and a titanium dioxide nanoparticle conjugated with crystal violet and folic acid (TiO₂-CV-rBSA-FA)," explains co-corresponding author Yujiao Xie.
Notably, the dual bioprobes are co-incubated to ensure their physical co-localization on the target CTC surface, thereby subjecting both the AR and CV reporters to identical environmental perturbations."
"By utilizing the characteristic peak intensity ratio (I_CV/I_AR), we achieved significantly enhanced signal reproducibility, reducing the RSD of SERS detection of breast cancer-derived CTCs from approximately 30% with a single bioprobe to approximately 10%," adds Xie.
Further, experimental results showed that the ratiometric platform achieves an LOD as low as 5 × 10⁻⁷ M. The individual bioprobes demonstrated excellent signal stability, with RSD values of 7.99% and 9.00%, respectively.
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Contact the author: Yujiao Xie, Aiguo Wu, Jie Lin, Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Laboratory of Advanced Theranostic Materials and Technology, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China, xieyujiao@nimte.ac.cn
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Journal
Nano Biomedicine and Engineering
Article Title
Ratiometric SERS platform of dual bioprobes for stable detection of circulating tumor cells
COI Statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.