Elsevier

Applied Surface Science

Volume 528, 30 October 2020, 146956
Applied Surface Science

Synthesis of CeBi0.4O3.7 nanofeather for ultrasensitive sandwich-like immunoassay of carcinoembryonic antigen

https://doi.org/10.1016/j.apsusc.2020.146956Get rights and content

Highlights

  • CeBi0.4O3.7 nanofeathers (CeBi0.4O3.7 NFs) were synthesized by doping Bi into CeO2 with preferable conductivity and biocompatibility.

  • CeBi0.4O3.7 NFs with gold nanoparticles (Au NPs) deposited on (Au@CeBi0.4O3.7 NFs) were successfully used as the surface recognition element to fabricate a sandwich-type immunosensor for ultrasensitive CEA detection.

  • The developed immunosensor exhibits as-expected electrochemical performance toward CEA in a wide concentration range with a low detection limit, favorable selectivity and high stability.

Abstract

Nonohybrids of CeBi0.4O3.7 with feather-like structures (CeBi0.4O3.7 NFs) were synthesized by incorporating Bi into CeO2, and thereby exhibiting preferable conductivity and biocompatibility. The modification of gold nanoparticles (Au NPs) further enhanced both properties of the obtained Au@CeBi0.4O3.7 NFs without changing the crystal structure, thereby benefiting the efficient immobilization of the secondary antibody (Ab2). The prepared Au@CeBi0.4O3.7 NFs were then used as a probe to label the Ab2. The reduced graphene oxide (rGO) with Au NPs deposited on Au-rGO was selected to modify the electrode for the immobilization of the first antibody, forming a sandwich-type Au@CeBi0.4O3.7 NF based electrochemical immunosensor to detect carcinoembryonic antigen (CEA). Such a Au@CeBi0.4O3.7 NF based sandwich immunosensor was successfully applied to detect CEA and exhibited, as expected, a linear response to CEA in a wide range of concentrations from 0.01 ng/mL to 100 ng/mL with a detection limit as low as 0.121 pg/mL, comparable to many existing immunosensors. Moreover, the favorable selectivity and stability make this immunosensor potentially applicable for the detection of CEA in real samples and this work provides new insights into the early detection of CEA.

Graphical abstract

CeBi0.4O3.7 nonohybrids with unique feather structure (CeBi0.4O3.7 NFs) were successfully synthesized by incorporating Bi into CeO2, showing preferable conductivity and biocompatibility. The modification of Au NPs (Au@CeBi0.4O3.7 NFs) further enhanced both properties without changing the structure of CeBi0.4O3.7 NFs. The as-prepared Au@CeBi0.4O3.7 NFs were used as an immunosensing probe to fabricate a sandwich-type electrochemical immunosensor for carcinoembryonic antigen (CEA) detection. This work provides new insights into the early detection of CEA.

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Introduction

Tumor markers are chemical structures that can be divided mainly into oncofetal proteins, tumor-associated antigens, enzymes and hormones. The concentration levels of tumor markers can reflect human health status and when they exceed a certain concentration range, it is likely that cancer can occur. For example, if the concentration of carcinoembryonic antigen (CEA) in the human body surpasses 5 ng/mL, cancer will probably develop [1], [2]. CEA is a broad-spectrum tumor marker, and mainly found in lung cancer, rectal cancer, esophageal cancer, gastric cancer, and pancreatic cancer [3], [4]. The most common current methods for the detection of CEA are enzyme-linked immunosorbent assays [5], [6], chemiluminescent immunoassays [7], [8], [9], [2] and electrochemical immunoassays [10], [11], [12], [13]. While the combination of electrochemical techniques with immunoassays is highly preferred because of their attractive properties such as high sensitivity and specificity, low detection limit, rapid current response, affordability and small sample consumption [14], [15], [16], [17], which are mostly dependent upon the properties of the nanomaterials involved, such as shape, size, conductivity, catalytic effect as well as their biocompatibility [18], [19], [20]. Therefore, the design and synthesis of nanomaterials, especially metal-based nanomaterials with advantages of nanoscale, high catalytic efficiency and good biocompatibility, is the focus of the development of electrochemical immunoassay.

In recent years, various metal-based nanomaterials with different shapes including nanoparticles [21], nanotubes [22], nanowires [23], and nanosheets [24] have been frequently used as probes to construct the electrochemical immunosensors. For example, Y. Zhuo et al. simultaneously detected CEA and AFP using a probe prepared by selecting Fe3O4 nanoparticle as the core, prussian blue as the interlayer and gold as the outer shell (Au-PB-Fe3O4) [25]. Furthermore, ZnO nanorods have been synthesized to produce an immunosensing platform for the detection of the bovine leukemia virus protein gp51 [26]. The nanocomposites of cuprous oxide@cericoxide and gold were used as labels to detect prostate specific antibody [27]. Currently, there are a variety of metal-based nanomaterials used to develop immunosensors for the detection of CEA, but the focus is mostly on the catalytic effect [28] and their biological toxicity is usually neglected, which represents another important factor affecting the practical application of immunosensors [29]. Therefore, the exploration of nanomaterials with low toxicity and preferred catalytic properties is essential for the detection of CEA. The metal cerium (Ce) is one of the most abundant rare earth elements and its electronic arrangement of its outermost layer is 4f15d16s2, making the valance states of Ce usually trivalent (CeIII) and tetravalent (CeIV) [30], endowing its oxides, especially CeO2 with many unique properties such as low toxicity, good biocompatibility, higher surface reaction rate, and high isoelectric point [31], [32], [33]. Besides, the catalytic activity and electrochemical characteristic of CeO2 are favorable for developing biosensors with high sensitivity. The application of CeO2 as an immunoassay probe has thus attracted a lot of attention from researchers [33], [34], [35]. For example, AFP has been detected using the composite of graphene oxide (GO) and mesoporous CeO2 modified Pd octahedral nanoparticles as the signal label for the Ab2 [35]. However, its application in the electrochemcial immunosensors has been significantly limited because of the unstable output signal, low electron conductivity, poor reproducibility and the increasing analytical time caused by the more heerogeneity and easy peeling off of CeO2 from the electrode surface [33]. To overcome these shortcomings, the essential electrode materials are required to possess high conductivity, suitable porous structures, high surface area and more exposed active sites. It remains highly desired so far.

Usually, the combination of two or more metals in a metal composition can change the size and shape of the hybrid materials and enhance their properties such as conductivity, bio-capability, stability or photo-catalytic capability due to the synergistic effect of metals [22], [36], [37], [38]. Bismuth (Bi) is an example of a heavy metal which is regarded as “friendly” to both humans and the environment, due to its extremely low toxicity [39], and it has therefore become an active research area in recent years because of its high oxygen ion conductivity, dielectric constant, and photoconductivity [40], [41]. To date, Bi-based materials such as bismuth oxide (Bi2O3) have been widely applied in the fields of photo-catalysis [42], photo-electrochemistry [43], capacitors [44] and electrochemical sensors [45]. Bi2O3, a layered semiconductor matter, has a narrow band gap of 2.8 ​eV, and thus shows relatively better conductivity than those with wide band gap[46], promising for high-performance electrochemical immunosensing. For example, mycotoxin was quantitatively detected through Bi2O3 nanorod modified indium-tin-oxide electrodes with significantly improved sensitivity [47]. On the other hand, Bi2O3 is an intrinsic p-type semiconductor with high hole mobility and can be used in electron donor catalytic processes [48]. Bi2O3 has been reported to be able to form a p-n heterojunction through coupling with n-type TiO2, and the formation of such heterojunction could increase the separation efficiency of photo-excited electron-hole pairs, leading to greatly enhanced photocurrent intensity [49]. As CeO2 is an intrinsic n-type semiconductor like TiO2 and often used for homogeneous catalysis [50], the coupling of Bi2O3 with CeO2 is predicted to improve both the signal response and the detection performance of the resulting bimetallic materials as label probe for the electrochemical immunoassay of CEA, with expected better biocompatibility and lower biotoxicity.

Herein, the feather-like CeBi0.4O3.7 nano-hybrid components (CeBi0.4O3.7 NFs) were synthesized by incorporating Bi into CeO2, whereupon both the conductivity and biocompatibility of CeBi0.4O3.7 NFs were found to be significantly enhanced as expected. Gold nanoparticles (Au NPs) were subsequently grown outside CeBi0.4O3.7 NFs (Au@CeBi0.4O3.7 NFs), forming an immunoassay probe of Au@CeBi0.4O3.7 NFs to label Ab2. At the same time, the reduced GO (rGO) with Au NPs deposited on the surface was utilized to modify the glass carbon electrode (GCE) (rGO-Au/GCE) to enhance the electron transfer on the surface of the GCE and capture the primary antibody (Ab1). Finally, a sandwich-type electrochemical immunosensor was fabricated using the Au@CeBi0.4O3.7 NFs labeled with Ab2 as the signal probe to detect CEA (Scheme 1), which exhibited high sensitivity, favorable selectivity and good stability, and provided a promising alternative for the detection of CEA.

Section snippets

Materials and apparatus

Details are provided in the supplemental materials section.

Synthesis of rGO and rGO-Au

The methods and processes for the preparation of rGO and rGO-Au are presented in the supplemental materials section.

Synthesis of the CeBi0.4O3.7 NFs

Briefly, 0.106 g of Bi(NO3)3·5H2O was dissolved in an ethylene solution of Ce(NO3)3 and stirred for 30 min; 0.125 g of CTAB was then added and stirring was continued. When the color of the solution became pale yellow, stirring was stopped. After this, 2.4 g of CO(NH2)2 was added and dispersed using sonication. The mixture

Characterizations of rGO and rGO-Au

In order to verify the transformation from GO to rGO, the FT-IR spectra of both GO (curve a) and rGO (curve b) curves were analyzed, as shown in Fig. S1A. In curve a, the peaks at 3403 cm−1, 1756 cm−1, 1616 cm−1, and 1062 cm−1 corresponded to the tensile vibration of O–H, Cdouble bondO, Cdouble bondC and C-O-C inside the GO, respectively. In comparison, the characteristic peaks of the oxy-functional groups within the rGO significantly decreased or even disappeared (curve b). The successful reduction of GO to rGO was

Conclusion

In summary, CeBi0.4O3.7 NFs were successfully synthesized by incorporating Bi into CeO2 and used as a probe after being decorated with Au NPs to produce a sandwich-type electrochemical immunosensor for the detection of CEA. The prepared CeBi0.4O3.7 NFs showed a unique nano-sized feather structure with a large surface area which could expose more active sites to the Ab2 and the conductivity of CeO2 was greatly improved by doping with Bi, due to the synergistic effect of the two metals. Both the

CRediT authorship contribution statement

Xinli Tian: Conceptualization, Methodology, Investigation, Writing - original draft. Penghui Cao: Validation. Dong Sun: Validation. Zhongmin Wang: Resources. Mengkui Ding: Resources, Data curation. Xiaoyu Yang: Resources, Data curation. Yuhao Li: Visualization. Ruizhuo Ouyang: Writing - review & editing, Funding acquisition. Yuqing Miao: Supervision.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was financially supported by the Natural Science Foundation of Shanghai (19ZR1434800, 19ZR1461900). The authors greatly appreciated these supports.

References (74)

  • H. Lv et al.

    Biosens. Bioelectron

    (2018)
  • J. Li et al.

    Biosens. Bioelectron.

    (2018)
  • X. Chen et al.

    Biosens. Bioelectron.

    (2013)
  • L. Zhao et al.

    Sens. Actuat. B Chem.

    (2018)
  • Z. Fu et al.

    Biosens. Bioelectron.

    (2008)
  • M. Liu et al.

    Talanta

    (2016)
  • H. Filik et al.

    Talanta

    (2019)
  • H. Filik et al.

    Talanta

    (2020)
  • A. Khanmohammadi et al.

    Talanta

    (2020)
  • S. Eissa et al.

    Biosens. Bioelectron.

    (2018)
  • C. Liu et al.

    Biosens. Bioelectron.

    (2018)
  • Z. Yang et al.

    Biosens. Bioelectron.

    (2017)
  • N. Lavanya et al.

    J. Colloid. Interface Sci.

    (2018)
  • Y. Li et al.

    Biosens. Bioelectron.

    (2017)
  • M. Hu et al.

    Sens. Actuat. B Chem.

    (2019)
  • J. Chen et al.

    Biosens. Bioelectron.

    (2018)
  • Y. Zhuo et al.

    Biomaterials

    (2009)
  • R. Viter et al.

    Sens. Actuat. B Chem.

    (2019)
  • F. Li et al.

    Biosens. Bioelectron.

    (2017)
  • Z. Tan et al.

    Bioelectrochemistry

    (2020)
  • L. Cui et al.

    J. Power Sources

    (2017)
  • T. Li et al.

    Sens. Actuat. B Chem.

    (2012)
  • N. Nesakumar et al.

    J Colloid Interf. Sci.

    (2013)
  • F. Charbgoo et al.

    Biosens. Bioelectron.

    (2017)
  • S. Yu et al.

    Talanta

    (2016)
  • Y. Wei et al.

    Biosens. Bioelectron.

    (2016)
  • Y. Ma et al.

    Electrochim. Acta

    (2019)
  • L. Yang et al.

    Biosens. Bioelectron.

    (2017)
  • V. Jovanovski et al.

    Curr. Opin. Electrochem.

    (2017)
  • M.K. Sharma et al.

    Biosens. Bioelectron.

    (2015)
  • S.N. Ding et al.

    Bioelectrochemistry

    (2010)
  • Y. Pang et al.

    Appl. Catal., B

    (2019)
  • W. Wang et al.

    Chem. Eng. J.

    (2019)
  • G.T. Zan et al.

    Energy Storage Mater.

    (2020)
  • P.R. Solanki et al.

    Mater. Sci. Eng. C Mater. Biol. Appl.

    (2017)
  • Y. Huang et al.

    Appl. Surf. Sci.

    (2017)
  • Y. Wang et al.

    Biosens. Bioelectron.

    (2019)
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