Quantification of Carcinoembryonic Antigen by Single Particle Inductively Coupled Plasma Mass Spectrometry
  
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KeyWord:single particle ICP-MS  ?AuNPs  ?magnetic beads  ?CEA evaluation
  
AuthorInstitution
HUANG Zi-li,HU Yue-li,LIU Jing,WU Yi,ZHAO Jin-yi,LIU Rui,L? Yi 1. Key Laboratory of Green Chemistry & Technology,Ministry of Education,College of Chemistry,Sichuan University,Chengdu ,China;2. Analytical & Testing Center,Sichuan University, Chengdu ,China
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Abstract:
      Cancer ranks as the leading threat to life expectancy all over the world,based on the latest estimations. Timely diagnosis and treatment of malignancies are still essential procedures to control the growing burden of cancer incidence and mortality.Single particle inductively coupled plasma mass spectrometry(spICP-MS) is a detection method for single particles in time-resolved mode.Inheriting the advantages of ICP-MS,spICP-MS ensures the single-particle counting with high sensitivity and high element resolutions.For immunoassays by this mode,there are breakthroughs not only in improving the detection limits of heterogeneous immunoassay but also in achieving multiplex homogeneous immunoassays with a simpler procedure.In this work,a single particle counting strategy was achieved by spICP-MS for sensitive carcinoembryonic antigen(CEA) evaluation.Gold nanoparticles(AuNPs) with a diameter of 50 nm were synthesized by one-step sodium citrate reduction,which were further applied to CEA-specific capturing. Anti-CEA antibody labeled AuNPs were synthesized by electrostatic adsorption between disulfide bonds exposed on the anti-CEA antibodies and the surface of AuNPs.The strategy was based on sandwich immunoassay where anti-CEA antibody labeled magnetic beads(MBs) were applied to capture CEA and antibody labeled AuNPs.After separation by a magnet,MBs were enriched at the bottom of the centrifugal tube,while the remaining AuNPs in the supernatant were counted by spICP-MS.The more CEA occurred in the sample,the more AuNPs probes were captured on the surface of MBs,and the fewer numbers of detectable remaining AuNPs were found in the supernatant.The proposed method was more direct and facile without washing steps,compared with the traditional MBs strategy.The experimental conditions were optimized,including magnetic beads volume applied in immunoassay and dilution ratio of the sample in spICP-MS.Under the optimal conditions,spICP-MS could accurately determine the change of AuNPs numbers in the process of CEA immunoassay,with an efficiency of 2.1%.The proposed method provided a three-orders-of-magnitude linear range(0.05-20 ng/mL,r2 = 0.997) with a limit of detection(LOD) as low as 0.017 ng/mL for CEA quantification.The method was also successfully utilized in serum sample analysis with good selectivity,exhibiting a great potential in cancer diagnosis.
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