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| Detection of Carcinoembryonic Antigen and Carbohydrate Antigen 15-3 in Human Breast Cancer Serum Using Single Particle Mode ICP-MS Coupled with Magnetic Immunoassay |
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| DOI： |
| KeyWord:inductively coupled plasma mass spectrometry(ICP-MS) nanoparticle carcinoembryonic antigen（CEA） carbohydrate antigen 15-3（CA15-3） serum |
| Author | Institution |
| HE Yong-yu,CAO Yu-pin,QIN Dong-miao,DENG Bi-yang |
1.State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources,School of Chemistry and Pharmaceutical Sciences,Guangxi Normal University,Guilin,China;2.College of Pharmacy,Guangxi University of Chinese Medicine,Nanning,China |
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| Abstract: |
| Carcinoembryonic antigen(CEA) is a kind of glycoprotein that has been extensively investigated as a tumor marker for clinical diagnosis,which is routinely used as part of an individuals annual medical checkup in China.It is present in about 95% of all colon tumors and 50% of breast tumors and is also associated with ovarian carcinoma,lung cancer and other cancers.CEA is a preferred tumor marker to help predict outlook in patients with colorectal cancer.Breast cancer is the most widespread life-threatening cancer among women worldwide.It is a complex and heterogeneous disease composed of several subtypes with different morphological and clinical implications.One of the most important biomarkers for breast cancer is the carbohydrate antigen 15-3(CA15-3).The concentration of CA15-3 in blood serum could provide information from monitoring of therapy,which could also predict breast cancer recurrence after curative surgery.Hence,it is important to develop a highly sensitive analytical method for accurate and selective detection of CEA and CA15-3.Compared to one element tagging,the immunoassay of multi-elements can improve assay efficiency and reduce sample consumption.In this study,several immunoassay procedure parameters were examined,including effects of dwell time,concentrations of CeO2-SiO2NPs and UCNPs on the number of detection events.A new method for simultaneous determination of CEA and CA15-3 was developed using single particle inductively coupled plasma mass spectrometry(ICP-MS) coupled with magnetic immunoassay.Meanwhile,amino-modified magnetic nanoparticles were synthesized and conjugated with primary CEA antibody and primary CA15-3 antibody to extract the target biomarkers.The suspension solutions were separated with a permanent magnet.Single particles were directly introduced into ICP-MS with a custom,gas pressure-assisted sample introduction system.Carboxyl-functionalized up-conversion nanoparticles(UCNPs) and amino-functionalized cerium dioxide-silicon dioxide nanoparticles(CeO2-SiO2NPs) were employed to tag antibodies.The frequencies of transient signals of 174Yb and 140Ce were directly related to the concentrations of UCNPs and CeO2-SiO2NPs.CEA and CA15-3 could be quantified via the frequency of transient signal produced by single particle ICP-MS.Under the optimal conditions,the linear concentration ranges for CEA and CA15-3 were 0.02-100 ng·mL-1 and 0.05-50 U·mL-1,respectively.Their correlation coefficients were 0.994 0 and 0.987 0,respectively.The detection limits(LOD,S/N=3) of CEA and CA15-3 were 0.006 7 ng·mL-1 and 0.016 7 U·mL-1,respectively.The method was applied to the simultaneous detection of CEA and CA15-3 in human breast cancer serum with recoveries of 95.2%-98.9% and 95.5%-97.2%,and relative standard deviations(RSD) of 3.0%-4.6% and 3.4%-4.3%,respectively. |
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