Carcinoembryonic antigen (CEA) is a cancer-related tumor marker, which is commonly used for preventive screening, auxiliary diagnosis, and recurrence monitoring. Therefore, it is of great significance to develop a new CEA detection method. In this paper, we developed an SERS aptasensor for CEA based on silver nanorod array chip, thiol aptamer, and 4-mercaptophenylboronic acid (4-MPBA). The silver nanorod array chip modified by CEA thiol aptamer (aptamer-SH) was used as SERS capture substrates. Ag@4-MPBA was used as a surface-enhanced Raman spectroscopy (SERS) tag. This proposed SERS aptasensor could detect CEA down to 0.447 pg·mL−1 with a wide linear range from 1 pg·mL−1 to 100 ng·mL−1 (R2 = 0.9907). The recovery of the standard addition test for CEA in serum was between 97.25% and 102.67%, and the RSD ≤ 2.52% (n = 3). The sensor has the advantages of good specificity, high sensitivity, and a wide linear range. It provides a new method for the detection of CEA in serum.
ShekariZ.ZareH.R.FalahatiA.. “Dual Assaying of Breast Cancer Biomarkers by Using a Sandwich-Type Electrochemical Aptasensor Based on a Gold Nanoparticles-3D Graphene Hydrogel Nanocomposite and Redox Probes Labeled Aptamers”. Sens. Actuators, B. 2021. 332: 129515.
2.
HottaT.TakifujiK.YokoyamaS.MatsudaK., et al. “Impact of the Post/Preoperative Serum CEA Ratio on the Survival of Patients with Rectal Cancer”. Surg. Today. 2014. 44(11): 2106‐2115.
3.
SiregarG.A.SibaraniH.. “Comparison of Carcinoembryonic Antigen Levels Among Degree of Differentiation and Colorectal Cancer’s Location in Medan”. Open Access Maced. J. Med. Sci2019. 7(20): 3447-3450.
4.
MengQ.ShiS.LiangC.LiangD., et al. “Diagnostic and Prognostic Value of Carcinoembryonic Antigen in Pancreatic Cancer: A Systematic Review and Meta-Analysis”. Oncotargets Ther. 2017. 10: 4591‐4598.
5.
StieberP.NagelD.BlankenburgI.HeinemannV., et al. “Diagnostic Efficacy of CA 15-3 and CEA in the Early Detection of Metastatic Breast Cancer: A Retrospective Analysis of Kinetics on 743 Breast Cancer Patients”. Clin. Chim. Acta. 2015. 448: 228‐231.
6.
ChonH.LeeS.SonS.W.OhC.H.ChooJ.. “Highly Sensitive Immunoassay of Lung Cancer Marker Carcinoembryonic Antigen Using Surface-Enhanced Raman Scattering of Hollow Gold Nanospheres”. Anal. Chem. 2009. 81(8): 3029‐3034.
7.
ZhouF.WangM.YuanL.ChengZ., et al. “Sensitive Sandwich ELISA Based on a Gold Nanoparticle Layer for Cancer Detection”. Analyst. 2012. 137(8): 1779‐1784.
8.
LanQ.RenC.LambertA.ZhangG., et al. “Platinum Nanoparticle-Decorated Graphene Oxide@Polystyrene Nanospheres for Label-Free Electrochemical Immunosensing of Tumor Markers”. ACS Sustain. Chem. Eng. 2020. 8(11): 4392‐4399.
9.
LiW.QiaoX.HongC.MaC.SongY.. “A Sandwich-Type Electrochemical Immunosensor for Detecting CEA Based on CeO2-MoS2 Absorbed Pb2”. Anal. Biochem. 2020. 592: 113566.
10.
LiX.WangR.ZhangX.. “Electrochemiluminescence Immunoassay at a Nanoporous Gold Leaf Electrode and Using CDTE Quantum Dots as Labels”. Microchim. Acta. 2011. 172(3‐4): 285‐290.
11.
PalS.BhandS.. “Zinc Oxide Nanoparticle-Enhanced Ultrasensitive Chemiluminescence Immunoassay for the Carcinoma Embryonic Antigen”. Microchim. Acta. 2015. 182(9‐10): 1643‐1651.
12.
ZhuJ.WangJ.-F.LiJ.-J.ZhaoJ.-W.. “Specific Detection of Carcinoembryonic Antigen Based on Fluorescence Quenching of Au–Ag Core-Shell Nanotriangle Probe”. Sens. Actuators, B. 2016. 233(42): 214‐222.
13.
ZhanY.YangS.LuoF.GuoL., et al. “Emission Wavelength Switchable Carbon Dots Combined with Biomimetic Inorganic Nanozymes for a Two-Photon Fluorescence Immunoassay”. ACS Appl. Mater. Interfaces. 2020. 12(27): 30085-30094.
14.
ChenA.YangS.. “Replacing Antibodies with Aptamers in Lateral Flow Immunoassay”. Biosens. Bioelectron. 2015. 71: 230-242.
YuH.AlkhamisO.CanouraJ.LiuY.XiaoY.. “Advances and Challenges in Small‐Molecule DNA Aptamer Isolation, Characterization, and Sensor Development”. Angew. Chem. Int. Ed2021. 60(31): 16800-16823.
18.
NimjeeS.M.RusconiC.P.SullengerB.A.. “Aptamers: An Emerging Class of Therapeutics”. Annu. Rev. Med. 2005. 56(1): 555-583.
19.
ZhangX.ZhuS.DengC.ZhangX.. “An Aptamer Based On-Plate Microarray for High-Throughput Insulin Detection by MALDI-TOF MS”. Chem. Commun2012. 48(21): 2689.
20.
ZhangY.YouY.XiaZ.HanX., et al. “Graphene Oxide-Based Selection and Identification of Ofloxacin-specific Single-Stranded DNA Aptamers”. RSC Adv. 2016. 6(101): 99540-99545.
21.
YangX.ZhuoY.ZhuS.LuoY., et al. “Selectively Assaying CEA Based on a Creative Strategy of Gold Nanoparticles Enhancing Silver Nanoclusters’ Fluorescence”. Biosens. Bioelectron. 2015. 64: 345-351.
22.
QiuZ.ShuJ.TangD.. “Bioresponsive Release System for Visual Fluorescence Detection of Carcinoembryonic Antigen from Mesoporous Silica Nanocontainers Mediated Optical Color on Quantum Dot-Enzyme-Impregnated Paper”. Anal. Chem. 2017. 89(9): 5152-5160.
23.
WangY.WeiZ.LuoX.WanQ., et al. “An Ultrasensitive Homogeneous Aptasensor for Carcinoembryonic Antigen Based on Upconversion Fluorescence Resonance Energy Transfer”. Talanta. 2019. 195: 33-39.
24.
ShuH.WenW.XiongH.ZhangX.WangS.. “Novel Electrochemical Aptamer Biosensor Based on Gold Nanoparticles Signal Amplification for the Detection of Carcinoembryonic Antigen”. Electrochemistry Communications. 2013. 37: 15-19.
25.
HuangJ.-Y.ZhaoL.LeiW.WenW., et al. “A High-Sensitivity Electrochemical Aptasensor of Carcinoembryonic Antigen Based on Graphene Quantum Dots-Ionic Liquid-Nafion Nanomatrix and DNAzyme-Assisted Signal Amplification Strategy”. Biosens. Bioelectron. 2018. 99: 28-33.
26.
JiangL.HassanM.M.AliS.LiH., et al. “Evolving Trends in SERS-Based Techniques for Food Quality and Safety: A Review”. Trends Food Sci. Technol. 2021. 112: 225-240.
27.
ZhangL.LianW.LiP.MaH., et al. “Crocein Orange G Mediated Detection and Modulation of Amyloid Fibrillation Revealed by Surface-Enhanced Raman Spectroscopy”. Biosens. Bioelectron. 2020. 148: 111816.
28.
ChenQ.QinL.ShiC.KangS.-Z.LiX.. “A Stable and Plug-and-Play Aluminium/Titanium Dioxide/Metal-Organic Framework/Silver Composite Sheet for Sensitive Raman Detection and Photocatalytic Removal of 4-Aminothiophenol”. Chemosphere. 2021. 282: 131000.
29.
ChakrabortyA.GhoshA.BaruiA.. “Advances in Surface-Enhanced Raman Spectroscopy for Cancer Diagnosis and Staging”. J. Raman Spectrosc. 2020. 51(1): 7-36.
30.
CuiJ.GuanQ.LvH.FuK., et al. “Three-Dimensional Nanorod Array for Label-Free Surface-Enhanced Raman Spectroscopy Analysis of MicroRNA Pneumoconiosis Biomarkers”. Spectrochim. Acta, Part A. 2021. 261: 120015.
31.
JinR.YanX.SunP.LuG.. “Dual-Signal Readout by Hybrid Nanoflowers for Point-of-Care Ultrasensitive Detection of Organophosphorus Pesticide”. ECS Meeting Abstracts. 2020. MA2020-01(27): 2021.
32.
GuoM.DongJ.XieW.TaoL., et al. “SERS Tags-Based Novel Monodispersed Hollow Gold Nanospheres for Highly Sensitive Immunoassay of CEA”. J. Mater. Sci. 2015. 50(9): 3329-3336.
33.
MedetalibeyogluH.KotanG.AtarN.YolaM.L.. “A Novel Sandwich-Type SERS Immunosensor for Selective and Sensitive Carcinoembryonic Antigen (CEA) Detection”. Anal. Chim. Acta. 2020. 1139: 100-110.
34.
LiL.LiuC.CaoX.TanL.LuW.. “Multiplexing Determination of Cancer-Associated Biomarkers by Surface-Enhanced Raman Scattering Using Ordered Gold Nanohoneycomb Arrays”. Bioanalysis. 2017. 9(20): 1561-1572.
35.
SongC.MinL.ZhouN.YangY., et al. “Ultrasensitive Detection of Carcino-Embryonic Antigen by Using Novel Flower-Like Gold Nanoparticle SERS Tags and SERS-Active Magnetic Nanoparticles”. RSC Adv. 2014. 4(78): 41666-41669.
36.
YangY.ZhuJ.WengG.-J.LiJ.-J.ZhaoJ.-W.. “Gold Nanoring Core-Shell Satellites with Abundant Built-In Hotspots and Great Analyte Penetration: An Immunoassay Platform for the SERS/Fluorescence-Based Detection of Carcinoembryonic Antigen”. Chem. Eng. J. 2021. 409: 128173.
37.
SongG.ZhouH.GuJ.LiuQ., et al. “Tumor Marker Detection with Surface Enhanced Raman Spectroscopy on 3D Au Butterfly Wings”. J. Mater. Chem. B. 2016. 5(8): 1594‐1600.
38.
LuT.WangL.XiaY.JinY., et al. “A Multimer-Based SERS Aptasensor for Highly Sensitive and Homogeneous Assay of Carcinoembryonic Antigens”. Analyst. 2021. 146(9): 3016-3024.
39.
ZhuC.MengG.ZhengP.HuangQ., et al. “A Hierarchically Ordered Array of Silver-Nanorod Bundles for Surface-Enhanced Raman Scattering Detection of Phenolic Pollutants”. Adv. Mater. 2016. 28(24): 4871-4876.
40.
PanM.SunY.ZhengJ.YangW.. “Boronic Acid-Functionalized Core–Shell–Shell Magnetic Composite Microspheres for the Selective Enrichment of Glycoprotein”. ACS Appl. Mater. Interfaces. 2013. 5(17): 8351-8358.
41.
ZhangS.HeX.ChenL.ZhangY.. “Boronic Acid Functionalized Magnetic Nanoparticles via Thiol-ENE Click Chemistry for Selective Enrichment of Glycoproteins”. New J. Chem. 2014. 38(9): 4212-4218.
42.
WangB.DuanA.XieS.ZhangJ., et al. “The Molecular Imprinting of Magnetic Nanoparticles with Boric Acid Affinity for the Selective Recognition and Isolation of Glycoproteins”. RSC Adv. 2021. 11(41): 25524-25529.
43.
YeJ.ChenY.LiuZ.. “A Boronate Affinity Sandwich Assay: An Appealing Alternative to Immunoassays for the Determination of Glycoproteins”. Angew. Chem. 2014. 126(39): 10554-10557.
44.
XieD.ZhuW.F.ChengH.YaoZ.Y., et al. “An Antibody-Free Assay for Simultaneous Capture and Detection of Glycoproteins by Surface Enhanced Raman Spectroscopy”. Phys. Chem. Chem. Phys. 2018. 20(13): 8881-8886.
45.
ZhouT.LuD.SheQ.ChenC.ChenJ., et al. . Hypersensitive Detection of IL-6 on SERS Substrate Calibrated by Dual Model”. Sens. Actuators, B. 2021. 336: 129597.
46.
HeY.LiL.LiX.LinC.ZhangY.. “Construction of Boronate-Affinity Magnetic Immunity SERS Sensor and Detection of Alpha-Fetoprotein (AFP) in Human Serum”. BCSJ. 2021. 94(3): 860-868.
47.
WangZ.LiW.ZhouZ.CuiY.. “Experimental Indication of Chemical Effects in Surface Enhanced Hyper Rayleigh Scattering Using Dye-Adsorbed Ag Nanoparticles”. Opt. Mater. 2011. 33(6): 920-923.
48.
PanY.WangL.DengY.WangM., et al. “A Simple and Sensitive Method for Exosome Detection Based on Steric Hindrance-Controlled Signal Amplification”. Chem. Commun. 2020. 56(89): 13768-13771.
49.
ZhangX.WangT.LiY.FuY.GuoL.. “Optimally Designed Gold Nanorattles with Strong Built-In Hotspots and Weak Polarization Dependence”. Nanotechnology. 2017. 28(49): 495201.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
