TiO2-based Surface-Enhanced Raman Scattering bio-probe for efficient circulating tumor cell detection on microfilter

Xiawei Xu, Jie Lin, Yanhong Guo, Xiaoxia Wu, Yanping Xu, Dinghu Zhang, Xiangzhi Zhang, Xie Yujiao, Jing Wang, Chengyang Yao, Junlie Yao, Jie Xing, Yi Cao, Yanying Li, Wenzhi Ren, Tianxiang Chen, Yong Ren, Aiguo Wu

Research output: Journal PublicationArticlepeer-review

19 Citations (Scopus)


Circulating tumor cell (CTC) detection as a burgeoning detection strategy can identify the tumor lesion in the early stage, and facilitates the understanding of tumorigenesis, tumor progression, metastasis, and drug-resistance. Herein, we present a novel strategy for in situ isolating and directly detecting CTCs from peripheral blood at single-cell resolution using black TiO2 (B–TiO2)-based Surface-Enhanced Raman Scattering (SERS) bio-probe on a microfilter. CTCs were isolated from blood by microfilter based on the size and deformation difference. The SERS bio-probe was composed of crystal-amorphous core-shell B–TiO2 nanoparticles (NPs), alizarin red (AR) as Raman reporter molecules, and a thin protective layer of NH2-PEG2000-COOH (PEG), which provided sufficient binding sites for target molecule of folic acid (FA). Demonstrated by three cell lines of MCF-7 (folate receptor (FR) positive), A549 and Raw264.7 (FR negative), SERS bio-probe of B–TiO2-AR-PEG-FA could distinguish FR positive CTCs from peripheral blood cells efficiently by targeting FR on CTC membranes and ruling out false positive interference of white blood cells (WBCs) with reliability and specificity. Benefiting by these advantages, this strategy enhanced the detection efficiency and veracity, which reduced the detection time within 1.5 h and make the LOD of detection reduced to 2 cells/mL. These features also facilitated successful CTC detection in several clinical cancer patient bloods which illustrates that the integration of microfluidic isolation and SERS detection may open new paths for liquid biopsy.

Original languageEnglish
Article number114305
JournalBiosensors and Bioelectronics
Publication statusPublished - 15 Aug 2022


  • CTC
  • High sensitivity
  • High specificity
  • Microfluidics
  • SERS

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biomedical Engineering
  • Electrochemistry


Dive into the research topics of 'TiO2-based Surface-Enhanced Raman Scattering bio-probe for efficient circulating tumor cell detection on microfilter'. Together they form a unique fingerprint.

Cite this