We describe a “turn-on” magnetic fluorescent biosensor based on graphene quantum dots (GQDs), Fe3O4, and molybdenum disulfide (MoS2) nanosheets. It is used for rapid, efficient, and sensitive separation and detection of circulating tumor cells (CTCs). A facile approach (electrochemical synthesis method) for the preparation of photoluminescent GQDs functionalized with an aptamer [epithelial cell adhesion molecule (EpCAM) receptors] and a magnetic agent for one-step bioimaging and enrichment of CTCs is described. MoS2 nanosheets, as a fluorescence quencher, and the aforementioned aptamer@Fe3O4@GQD complex were assembled to construct “turn-on” biosensing magnetic fluorescent nanocomposites (MFNs). This system exhibits low cytotoxicity and an average capture efficiency of 90%, which is higher than that of other magnetic nanoparticles on account of the one-step CTC separation method. In addition, the MFNs could quickly identify and label CTCs within 15 min, surpassing other one-step and two-step marker detection methods. Furthermore, because of the presence of aptamers, the MFNs have specific capability to capture CTCs (both low- and high-EpCAM-expressing cells). In addition, high-sensitivity detection of up to ten tumor cells in whole blood was achieved. Therefore, the MFNs have great potential to be used as universal biosensing nanocomposites for fluorescence-guided tumor cell enrichment and bioimaging.
Graphene quantum dots Aptamer Circulating tumor cells Magnetic fluorescence biosensor Magnetic separation
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This work was supported by the National Research Program of China (201513006, 31371768, 2016YFD0401204), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_1413), the Collaborative Innovation Center for Food Safety and Quality Control, the Priority Academic Development Program of Jiangsu Higher Education Institutions, and the Agricultural science and technology innovation projects of Shanxi province, China (2015NY002).
Compliance with ethical standards
This study was approved by the Institute of Jiangnan University Medical Ethics Committee, and the investigation was performed according to the ethical guidelines in document no. JNUMEC-201801008, October 2018.
Informed consent was obtained from all individual participants included in the study. All blood samples were obtained from healthy volunteers.
Conflict of interest
The authors declare that they have no competing interests.
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1.School of Food Science, State Key Laboratory of Food Science and Technology, National Engineering Research Center for Functional Foods, School of Food Science Synergetic Innovation Center of Food Safety and NutritionJiangnan UniversityWuxiChina
2.Department of Toxicology, Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, School of Public HealthNanjing Medical UniversityNanjingChina
3.National Institutes for Food and Drug ControlBeijingChina
4.Guangzhou GRG Metrology & Test Co. LtdGuangzhouChina
5.School of Food and Biological EngineeringShaanxi University of Science and TechnologyXi’anChina