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Ni-MOF nanosheet microflowers
Sensors & Actuators: B. Chemical 311 (2020) 127919
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A highly sensitive and stable electrochemiluminescence immunosensor for alpha-fetoprotein detection based on luminol-AgNPs@Co/Ni-MOF nanosheet microflowers
T
Shanshan Wanga,b, Minmin Wangb,c, Chuanping Lib,c, Haijuan Lib,*, Chunhua Gea,*, Xiangdong Zhanga, Yongdong Jinb,c,* a b c
College of Chemistry, Liaoning University, Shenyang 110036, China State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China University of Chinese Academy of Sciences, Beijing 100049, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Electrochemiluminescence Metal-organic framework Label-free immunosensor Alpha–fetoprotein
Due to their high catalytic effect on the electrochemiluminescence (ECL) of luminol, noble metal nanoparticles (NPs) have been widely used in luminol-based ECL immunosensors. However the aggregation of NPs often resulted in the decrease of ECL signal and affected the stability and durability of the sensor. In this study, a microflower-like structure made of ultrathin Co/Ni-based metal-organic frameworks (MOF) nanosheets were used as a platform for luminol-functionalized AgNPs to construct an immunosensor for tumor marker alphafetoprotein. The nanosheet and microflower-like assembly structure of the Co/Ni-MOF greatly improved the ECL performance of the luminol-AgNPs system, attributed to their large surface area, resistance to particle agglomeration and the high catalytic activity of the Co/Ni-MOF. The ultrathin Co/Ni-MOF was full of atomically dispersed cobalt ions and nickel ions, which can catalyze the ECL reaction of luminol and H2O2. The as-fabricated immunosensor has a good sensitivity with detection limit of 0.417 pg mL−1 (S/N=3), and shows satisfactory performance in practical applications.
1. Introduction Electrochemiluminescence (ECL), the combination of chemiluminescence and electrochemistry, possessing the advantage of both technologies, such as low background signals, wide dynamic range, high sensitivity, easy control and simple device, is a powerful tool in immunoassays and clinical diagnosis [1–11]. Due to its high luminous efficiency and low excitation potential, luminol is one of the most widely used ECL reagents. And as luminol is a reducing reagent, it has been frequently used to synthesize luminol-functionalized noble metal NPs. These NPs have a high catalytic effect on luminol ECL reactions. In addition to noble metal NPs, metal ions are also used to enhance the ECL intensity of luminol as they can catalyze the reaction between luminol and H2O2 [12–14]. For example, Cui et al. synthesized gold NPs bifunctionalized by luminol and Co2+-based metal complexes [15], in which the introduction of Co2+ complexes greatly enhanced the ECL of luminol-AuNPs. Although noble metal NPs possess high catalytic effect on luminol ECL, the aggregation/agglomeration of NPs in the electrochemical
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process often influences the long stability of ECL sensors. To prevent the agglomeration of NPs and to further improve the ECL behavior, nanomaterials with large surface area and catalytic properties were used as platforms to support luminol-AuNPs, such as molybdenum carbides [16], ZnO [17], graphite-like carbon nitride [18], graphene [19] etc. Cui et al. constructed a label-free aptasensor for TNT based on 2D bilayer structure of luminescence and catalytic functionalized graphene and graphene oxides [19]. The aptasensor has a low detection limit of 0.63 pg mL−1 for TNT, but the construction procedure was a bit complicated, in which N-(aminobutyl)-N-(ethylisoluminol)/hemin dualfunctionalized graphene hybrids and luminol functionalized silver/ graphene oxide composite were both employed. MOFs represent a diversity of highly porous materials wherein metal cations are connected by organic linkers [20–24]. Attributed to their abundant porosity and large internal surface areas, MOFs are widely used in areas of gas storage, separation, catalysis, and recently in ECL detections. For example, Yuan et al. synthesized a novel mesoporous luminescence-functionalized MOF (Ru–PCN-777) with high stability and excellent ECL performance, and constructed it into an
Corresponding authors. E-mail addresses: [email protected] (H. Li), [email protected] (C. Ge), [email protected] (Y. Jin).
https://doi.org/10.1016/j.snb.2020.127919 Received 31 October 2019; Received in revised form 16 February 2020; Accepted 24 February 2020 Available online 26 February 2020 0925-4005/ © 2020 Elsevier B.V. All rights reserved.
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were purchased from Shanghai Linc-Bio Science Co. LTD (Shanghai, China) while other proteins such as D-biotin, immunoglobulin G (IgG), bovine serum albumin (BSA) and myoglobin (Mb) were obtained from Sinopharm Chemical Reagent Co. Ltd. (Beijing, China). The H2O2 solution were freshly prepared from 30 % H2O2 (Xinke Electrochemical Reagent Factory, Bengbu, China) for daily use. Water was purified with a Millipore system and 0.1 M phosphate buffered saline (PBS) with pH of 7.4 was used for incubation. All of other reagents were of analytical grade.
immunosensor for mucin 1 detection [22]. Shao et al. developed a onestep strategy for fabrication of tris (bipyridine) ruthenium (II)-functionalized MOF (Ru-MOF) thin films using a self-assembly approach assisted by an electrochemical way. The Ru-MOF modified electrode was used to detect human heart-type fatty-acid-binding protein with great selectivity and stability [23]. Our group developed a ZIF-67 enhanced label-free ECL immunosensor for cardiac troponin I, the introduction of Co-based MOF greatly enhanced the sensitivity of the immunosensor [24]. As an oncofetal glycoprotein, alpha fetoprotein (AFP) has a low concentration in normal adult serum, and when it exceeded 20 ng mL−1, it is an early indicator of Hepatocellular carcinoma. Being one of the most important tumor marker for liver cancer, researchers have endeavored much effort in detecting AFP. Due to its high sensitivity and selectivity, simple equipment and low cost, immunoassays based on ECL and electrochemistry have attracted more and more attention. For example, Luo and coworkers developed recently a novel label-free electrochemical immunosensor for AFP based on oxygen reduction reaction [25]. In their study, rhombic dodecahedral Cu3Pt nanoframe was used as a high efficient catalyst for oxygen reduction reaction, which acts as a signal amplification platform for the immunosensor and guarantees its high sensitivity. In this study, a microflower-like structure made of ultrathin Co/NiMOF nanosheets and luminol-functionalized AgNPs was used as a superior ECL platform for immunosensor (Scheme 1). The microflowerlike assembly structure of the Co/Ni-MOF nanosheet has greatly improved the ECL performance of the luminol-AgNPs system, due to their large surface area, resistance to particle agglomeration and the high catalytic activity. Furthermore, the micro-/nano-structured composites of luminol-AgNPs@Co/Ni-MOF were used to construct a label-free immunosensor for AFP. The as-fabricated immunosensor has a low detection limit (0.417 pg mL−1, S/N = 3) towards AFP and a wide linear range from 1 pg mL−1 to 100 ng mL−1. The sensor has a good selectivity and showed satisfactory performance in serum sample detections.
2.2. Synthesis of luminol-AgNPs Luminol-functionalized AgNPs (luminol-AgNPs) were synthesized according to the previous reports [26,27]. The procedures were as follows: firstly, 3 mL of 5 mM AgNO3 was added to a solution containing 5 mL of ultrapure water and 9 mL of absolute ethanol and stirred vigorously. Then, 0.5 mL of 0.01 M luminol in 0.1 M NaOH was added to the mixture as soon as possible to get a yellow solution. All these procedures were conducted at room temperature and kept stirring continuously for 2 h with the color changed from light yellow to dark yellow, indicating the successful formation of luminol-AgNPs. Finally, after centrifugation at 10,000 rpm for 10 min, the soft sediment was obtained for further use. 2.3. Synthesis of ultrathin Co/Ni-MOF nanosheet microflowers The ultrathin Co/Ni-MOF was synthesized according to the following steps [28]. Briefly, 9 mmol of Co(NO3)2·6H2O and 1 mmol Ni (NO3)2·6H2O were dissolved in 30 mL of methanol to form solution A. Then, 3 mmol of 2-methylimidazole was dissolved in 10 mL of methanol to form solution B. The two solutions were mixed and stirred for 2 min, then kept static at room temperature for 24 h. After that the solution was centrifuged and washed by methane for three times. 2.4. Deposition of luminol-AgNPs on the surface of Co/Ni-MOFs As indicated in dynamic light scattering data (Figure S4), the surfaces of luminol-AgNPs and Co/Ni-MOF were oppositely charged, so luminol-AgNPs can be adsorbed on the surface of Co/Ni-MOF nanosheet microflowers by electrostatic interaction. The composites of luminol-AgNPs@Co/Ni-MOF were obtained by mixing luminol-AgNPs with Co/Ni-MOF and shook vigorously.
2. Experimental section 2.1. Chemical and reagents Luminol and AgNO3 were obtained from Sigma-Aldrich (Milwaukee, WI, USA). 2-methylimidazole (MeIM), Co(NO3)2 and Ni (NO3)2 were purchased from Aladdin. Both biotin-anti-AFP and AFP
2.5. Fabrication of the ECL immunosensor for AFP detection Before the fabrication, the gold electrode was polished with 1 μm and 0.3 μm alumina in turn. After ultrasonicated in ultra-pure water for 5 min and rinsed with ultra-pure water for several times, the electrode was dried with inert gas argon to get a mirror-like surface. Then the electrode was scanned in 1 M H2SO4 at a scan rate of 0.5 V/s in the potential range between -0.4 V and 1.6 V versus Ag/AgCl using cyclic voltammetry (CV) until a reproducible CV was obtained, and the electrode was rinsed with distilled water for further uses. Finally, the electrode was irradiated with a novascan PSD Pro series UV ozone cleaning system for 30 min prior to sensor construction. Next, the cleaned gold electrode was incubated in 1,3-propanedithiol solution overnight to obtain the Au-S bond. After rinsed with ethanol and ultrapure water, 2 μL of as-prepared luminol-AgNPs@Co/ Ni-MOF was dropped on the surface of the electrode. Then the electrode was dried at room temperature, and 2 μL of biotin-anti-AFP solution was dropped and incubated at 4 °C for 12 h. To block the remaining binding sites, 2 μL of 1 % BSA was placed onto the electrode. After rinsed with 0.1 M PBS buffer (pH = 7.4), the BSA/biotin-anti-AFP/ luminol-AgNPs@Co/Ni-MOF/1,3-propanedithiol/Au electrode was formed and stored at 4 °C for use.
Scheme 1. Sensing mechanism and the fabrication procedures of the microflower-like luminol-AgNPs@Co/Ni-MOF based immunosensor for the detection of AFP. 2
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(TEM) in Fig. 1. As seen from atomic force microscopy (AFM) measurement of the ultrathin Co/Ni-MOF nanosheets in Figure S1, the thicknesses of the Co/Ni-MOF nanosheets was as thin as ∼ 1 nm, which will facilitate catalytic reactions due to the existence of rich coordinative unsaturated metal sites on the surfaces. The specific surface area and pore diameter of the Co/Ni-MOF were measured by Brunauer Emmett Teller (BET) adsorption isotherm and Barrett–Joyner–Halenda (BJH) methods. As shown in Figure S2, the specific area and pore size distribution of the Co/Ni-MOF were obtained to be ∼ 97.25 m2/g and 3.75 nm, respectively, indicating a mesoporous structure. LuminolAgNPs were prepared according to previous report [26,27]. As shown in Figure S3, the diameter of the luminol-AgNPs was about 33 nm. Since the surface of Co/Ni-MOF nanosheets and luminol-AgNPs were oppositely charged (Figure S4), the luminol-AgNPs can easily decorate on the surface of Co/Ni-MOF nanosheets by electrostatic interactions. As shown in Fig. 1(C–I), luminol-AgNPs were uniformly dispersed on the surface of Co/Ni-MOF nanosheets. The successful adsorption of luminol-AgNPs on Co/Ni-MOF nanosheets was further confirmed by UV–vis spectrum and X-ray photoelectron spectra (XPS), respectively. As shown in Fig. 2, for pure luminol, characteristic UV–vis absorbance peaks were appeared at about 200 nm, 230 nm, 305 nm and 350 nm; while luminol-AgNPs showed absorbance peaks at 220 nm, 290 nm, 365 nm and 425 nm, the characteristic of luminol and AgNPs. The luminol-AgNPs@Co/Ni-MOF complex exhibited the characteristic absorbance peak of Co/Ni-MOF nanosheets at 215 nm and two peaks of luminol-AgNPs at 365 nm and 420 nm, respectively [26,27], indicating that luminol-AgNPs were successfully incorporated with Co/Ni-MOF nanosheets. The components and the elements valences of the Co/NiMOF nanosheets were further characterized by XPS measurements (Figure S5). The XPS peaks located at 781.35 eV and 873.15 eV were assigned to Co 2p and Ni 2p state in Co/Ni-MOF nanosheets. The Co 2p and Ni 2p spectra can be extended to 780.75 eV (Co2+ ions) and 796.5 eV (Co3+ ions), 855.6 eV (Ni2+ ions) and 873.15 eV (Ni3+ ions) respectively, indicating that both cobalt and nickel were present in the form of divalent state [28–30]. Compared with the XPS survey of Co/ Ni-MOF, two new peaks located at 368.08 eV and 374.08 eV caused by Ag 3d [31] were observed in the XPS survey of luminol-AgNPs@Co/NiMOF, indicating that the luminol-AgNPs were successfully confined on the surface of Co/Ni-MOF nanosheets. Moreover, the present of Ag
2.6. ECL detection of AFP with the immunosensor A certain concentration of AFP was dropped on the surface of modified gold electrode and incubated for about 30 min. After dried at room temperature, the electrode was rinsed by 0.1 M PBS buffer (pH = 7.4) to remove the excess AFP. Then the modified gold electrode was used as the working electrode for ECL detection, Ag/AgCl (saturated KCl) electrode was connected as the reference electrode, and Pt wire was used as counter electrode. Using the three-electrode system, the ECL experiments were conducted with CV scanning from -1.3 to 1.3 V, the prepared immunosensor was placed in an ECL detector cell containing 700 μL of H2O2 in 0.1 M PBS (pH = 9) to measure the ECL intensity of the sensor. 2.7. Characterizations Transmission electron microscopy (TEM) images were obtained using a Hitachi 600 transmission electron microscope at an acceleration voltage of 100 kV (Hitachi, Tokyo, Japan). X-ray photoelectron spectroscopy (XPS) measurements were performed on an Escalab 250Xi, Thermo Fisher Scientific. Scanning electron microscope (SEM) images were obtained using XL30 ESEM FEG SEM (Philips, Netherlands). UV–vis absorption spectra were performed using a Lambda 750 spectrophotometer (Perkin-Elmer). The Zeta potential values of Co/Ni-MOF and luminol-AgNPs were taken from the Zeta sizer Nano-Z system (Malveren Instruments). The cyclic voltammetry of the electrode was conducted by an electrochemical workstation (CHI660E, Chenhua, Shanghai), and the ECL signal of the electrode was obtained by MPI-A capillary electrophoresis ECL system (Xi'an Ruimai Electronics Co., Ltd., Xi'an, China). 3. Results and discussions 3.1. Characterization of the luminol-AgNPs@Co/Ni-MOF complex First, the ultrathin Co/Ni-MOF nanosheets were prepared by the method mentioned before [28]. The obtained Co/Ni-MOF nanosheets showed a flower-like layered assembly structure as seen from scanning electron microscopy (SEM) and transmission electron microscopy
Fig. 1. Overall and partially enlarged SEM images (A) and typical TEM images of the as-prepared microflower-like Co/Ni-MOF (B). Typical TEM images of luminolAgNPs@Co/Ni-MOF (C). TEM images and elemental mapping analyses of a single luminol-AgNPs@Co/Ni-MOF particle (D-I). 3
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Fig. 2. UV/Vis absorption spectra of luminol-AgNPs (a), Co/Ni-MOF (b), luminol-AgNPs@Co/Ni-MOF (c) and luminol (d).
Fig. 4. Effect of the ratio (A) of Co/Ni-MOF to luminol-AgNPs on ECL intensity in 0.1 M PBS (pH = 7.4) containing 0.1 mM H2O2. Photomultiplier tube: 800 V. Effect of pH value (B) of the solution with 0.1 M PBS containing H2O2. Photomultiplier tube: 500 V.
enhancement. Most importantly, the ultrathin nanosheets and microflower-like assembly structure were good platform for supporting luminol-AgNPs, which effectively prevent the agglomeration of luminolAgNPs during electrochemical process. Moreover, the atomically dispersed Co and Ni ions in the MOF structure can facilitate the catalysis reaction between luminol and H2O2. The high catalytic effect of Co/NiMOF was further confirmed by CVs on the luminol-AgNPs modified electrode. As shown in Fig. 3B, for the luminol-AgNPs modified electrode, there were mainly three groups of redox peaks; the oxidization peak at ∼ 0.4 V and redox peaks at ∼ 0.2 V and 0.1 V were caused by the oxidation and reduction of AgNPs [31]. The redox peak at about -0.3 V to -0.4 V was observed which was attributed to the reduction of H2O2 and O2; this peak was decreased at N2 saturated atmosphere, confirmed that O2 was also reduced at the cathode electrode (Figure S10). The redox peak at around 1.0 V can be ascribed to oxidation and reduction of the gold electrode. After combined with Co/Ni-MOF nanosheets, the redox peaks of AgNPs were covered by Co/Ni-MOF, but the reduction of H2O2 and O2 was enhanced a lot which indicated that the integration of Co/Ni-MOF catalyzed the reduction of H2O2 and O2; while the redox of gold electrode was greatly enhanced and a new reduction peak at around -1.0 V was appeared which can be ascribed to the H2 evolution catalyzed by Co/Ni-MOF nanosheets. The ECL reached its highest intensity at ∼ 0.5 V (Fig. 3A), which is consistence with the electrocatalytic oxidation of luminol [32]. Besides H2O2, O2 is also an important coreactant of luminol ECL [15,32]; the dissolved oxygen and H2O2 were reduced to OOH− at about −0.4 V, while during the reverse scan, OOH− was electro-oxidized to O2%‾, which reacts with the luminol anion to produce excited-state species, and emits light.
Fig. 3. ECL intensity-potential curves (A) and cyclic voltammograms (B) of luminol-AgNPs@Co/Ni-MOF and luminol-AgNPs in the solution of 0.1 M PBS (pH = 7.4) containing 0.1 mM H2O2.
element in the quantitative assessment (Figure S7&S8) also confirmed the successful attachment of luminol-AgNPs on the surface of Co/NiMOF nanosheets.
3.2. CV and ECL behavior of the luminol-AgNPs@Co/Ni-MOF complex As shown in Fig. 3A, the ECL intensity of luminol-AgNPs@Co/NiMOF complex was about 3 times higher than that of luminol-AgNPs alone in the same condition. In order to investigate the enhancement mechanism of the Co/Ni-MOF on the ECL of luminol, the ECL behavior of the luminol-AgNPs modified gold electrode was studied in the presence of free Co2+ and Ni2+ with same content of that in Co/Ni-MOF (obtained by ICP MS) in the electrolyte solution. The electrode showed ∼ 1.69 times enhancement on the ECL intensity (Figure S9), which indicated that the structure of the Co/Ni-MOF affected a lot on the ECL
3.3. ECL detection of AFP To demonstrate sensing applicability of the luminol-AgNPs@Co/Ni4
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Fig. 6. ECL responses (A) and corresponding calibration curve (B) of ECL intensity to the logarithmic AFP concentration in 0.1 M PBS (pH = 9) buffer containing 0.1 mM H2O2.
Fig. 5. CV characterizations (A) in 0.1 M KCl containing 5.0 mM K3Fe(CN)6 aqueous solution and ECL responses (B) in 0.1 M PBS solution (pH = 9) containing 0.1 mM H2O2 for each modification step on gold electrode: (a) gold electrode/ 1,3-propanedithiol, (b) gold electrode/ 1,3-propanedithiol/ luminolAgNPs@Co/Ni-MOF, (c) gold electrode/ 1,3-propanedithiol/ luminolAgNPs@Co/Ni-MOF/ biotin-anti-AFP, (d) gold electrode/ 1,3-propanedithiol/ luminol-AgNPs@Co/Ni-MOF/ biotin-anti-AFP/ BSA, (e) gold electrode / 1,3propanedithiol / luminol-AgNPs@Co / Ni-MOF / biotin-anti-AFP / BSA/AFP, (f) bare gold electrode.
MOF, a label-free immunosensor was built to detect AFP. Before the construction of the immunosensor, the ratio of Co/Ni-MOF to luminolAgNPs and the pH of the solution were optimized. As shown in Fig. 4, the ratio of Co/Ni-MOF to luminol-AgNPs was adjusted from 0.3:1 to 2:1, the ECL intensity reach the highest at the ratio of 0.5:1. This may be caused by poor conductivity of the MOF which will decrease ECL intensity after the ratio higher than 0.5:1 [33,34]. It has been reported that the pH of ECL solution affects a lot on the ECL reaction [35–37]; suitable concentrations of OH− is helpful to generate O2%‾, so for most of luminol ECL, optimal reaction conditions occur under alkaline conditions. In this study, the pH of solution was adjusted from 7 to 10 and the highest ECL intensity was achieved at the pH of 9, which is accordance to the previous reports [36]. So, the ratio of Co/Ni-MOF to luminol-AgNPs as 0.5:1 and the pH 9 of the solution were chosen for the further ECL experiments. After optimizing the detection conditions, the label-free AFP immunosensor was constructed and the procedures were depicted in Scheme 1. Briefly, 1,3-propanedithiol was first used to connect luminolAgNPs@Co/Ni-MOF to the Au electrode, biotin-anti-AFP was linked to AgNPs via the formation of Ag-S bond. After that, BSA was used to block the residual nonspecific binding sites [37]. The modification procedure was monitored by CVs scanned in 0.1 M KCl solution containing 5 mM K3Fe(CN)6. As shown in Fig. 5A, the redox peak current was decreased rapidly after the modification of 1,3-propanedithiol on Au electrode surface, due to the retardation of electron transfer by 1,3propanedithiol. After the modification of luminol-AgNPs@Co/Ni-MOF, new peaks appeared at ∼ 0.1 V and -0.05 V which is related to the redox of luminol-AgNPs [31,38]. After incubated successively with
Fig. 7. (A) Selectivity of the AFP ECL immunosensor measured at pH 9. The concentrations of D-biotin, Mb and IgG were 10 ng mL−1, while the concentration of AFP was 1 ng mL−1. The mixture contains all the above proteins. (B) Stability of the immunosensor toward 10 ng mL−1 AFP based on continuous cyclic scanning in 0.1 M PBS (pH = 9) solution containing 0.1 mM H2O2.
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Declaration of Competing Interest
biotin-anti-AFP, BSA and AFP, the proteins blocked the electron transfer of the electrode which made the current density decreased gradually in 0.1 M PBS (pH = 7.4), as shown in Figure S11. In addition to CV characterizations, the ECL intensity variation of each modification step of electrodes was also monitored. As shown in Fig. 5B, bare gold electrode and the 1,3-propanedithiol modified gold electrode exhibited no ECL response, while after modified with the luminolAgNPs@Co/Ni-MOF, there was a prominent ECL peak. After the incubation with biotin-anti-AFP, BSA and AFP, the ECL intensity decreased in succession due to the blocking of electron transfer by the proteins as confirmed by CV characterizations. Based on the drop in ECL signal in the presence of AFP, we can calculate the concentration of AFP. As shown in Fig. 6, with the concentration of AFP increased from 1 pg mL−1 to 100 ng mL−1, the ECL intensity of the immunosensor decreased correspondingly. The regression equation was I = 821.41lgc – 5385.8 and the correlation coefficient was 0.988, where I was ECL intensity and c was the concentration of AFP (g/mL) [16]. The detection limit was 0.417 pg mL−1 at a signal-to-noise ratio of 3 (S/ N = 3). We have compared that with other reported methods in Table S1; the sensor based on our method is comparable with other methods and previous ECL methods. Three interfering proteins (IgG, Mb, Dbiotin) were further chosen to check the selectivity of the immunosensor. The concentration of IgG, Mb, D-biotin were all 10 ng mL−1, and the concentration of AFP was chosen as 1 ng mL−1. As shown in Fig. 7A, the ECL intensity decreased only in the presence of AFP and the mixture containing AFP, indicating good selectivity of the immunosensor. Fig. 7B shows the stability test of the as-prepared immunosensor with 10 ng mL−1 AFP in 0.1 M PBS (pH = 9) buffer containing 0.1 mM H2O2, the relative standard deviation (RSD) was 1.25 %, manifesting the good stability of the constructed immunosensor.
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. CRediT authorship contribution statement Shanshan Wang: Methodology, Writing - original draft. Minmin Wang: Methodology, Data curation. Chuanping Li: Data curation. Haijuan Li: Conceptualization, Writing - review & editing. Chunhua Ge: Supervision. Xiangdong Zhang: Supervision. Yongdong Jin: Conceptualization, Writing - review & editing, Supervision, Funding acquisition, Project administration. Acknowledgments This work was supported by the National Key Research and Development Program of China Grant No. 2016YFA0201300, the National Natural Science Foundation of China grant Nos. 21675146 and 21475125), and the Instrument Developing Project of the Chinese Academy of Sciences (Grant No. YZ201666). We are pleased to acknowledge the generous support of ECL instrument by Prof. Guobao Xu. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.snb.2020.127919. References [1] M.M. Richter, Electrochemiluminescence (ECL), Chem. Rev. 104 (2004) 3003–3036. [2] L.-Z. Hu, G.-B. Xu, Applications and trends in electrochemiluminescence, Chem. Soc. Rev. 39 (2010) 3275–3304. [3] K. Muzyka, M. Saqib, Z.-Y. Liu, W. Zhang, G.-B. Xu, Progress and challenges in electrochemiluminescent aptasensors, Biosens. Bioelectron. 92 (2017) 241–258. [4] Z.-Y. Liu, W.-J. Qi, G.-B. Xu, Recent advances in electrochemiluminescence, Chem. Soc. Rev. 44 (2015) 3117–3142. [5] L. Cui, J. Wu, H.-X. Ju, Electrochemical sensing of heavy metal ions with inorganic, organic and bio-materials, Biosens. Bioelectron. 63 (2015) 276–286. [6] S.-Y. Deng, H.-X. Ju, Electrogenerated chemiluminescence of nanomaterials for bioanalysis, Analyst 138 (2013) 43–61. [7] S.-J. Xu, Y. Liu, T.-H. Wang, J.-H. Li, Positive potential operation of a cathodic electrogenerated chemiluminescence immunosensor based on luminol and graphene for cancer biomarker detection, Anal. Chem. 83 (2011) 3817–3823. [8] H.-R. Zhang, M.-S. Wu, J.-J. Xu, H.-Y. Chen, Signal-on dual-potential electrochemiluminescence based on luminol-gold bifunctional nanoparticles for telomerase detection, Anal. Chem. 86 (2014) 3834–3840. [9] A. Karsten, F.M. Pravda, G.G. Guilbault, Recent applications of electrogenerated chemiluminescence in chemical analysis, Talanta 54 (2001) 531–559. [10] H.-M. Wang, C.-C. Wang, A.-J. Wang, L. Zhang, X.-L. Luo, P.-X. Yuan, J.-J. Feng, Green synthesis of Pd nanocones as a novel and effective electrochemiluminescence illuminant for highly sensitive detection of dopamine, Sens. Actuators B Chem. 281 (2019) 588–594. [11] H.-M. Wang, Y. Fang, P.-X. Yuan, A.-J. Wang, X.-L. Luo, J.-J. Feng, Construction of ultrasensitive label-free aptasensor for thrombin detection using palladium nanocones boosted electrochemiluminescence system, Electrochim. Acta 310 (2019) 195–202. [12] X.-B. Feng, N. Gan, H.-R. Zhang, Q. Yan, T.-H. Li, Y.-T. Cao, F.-T. Hu, H.-W. Yu, Q.L. Jiang, A novel “dual-potential” electrochemiluminescence aptasensor array using CdS quantum dots and luminol-gold nanoparticles as labels for simultaneous detection of malachite green and chloramphenicol, Biosens. Bioelectron. 74 (2015) 587–593. [13] X.-Y. Jiang, Y.-Q. Chai, H.-J. Wang, R. Yuan, Electrochemiluminescence of luminol enhanced by the synergetic catalysis of hemin and silver nanoparticles for sensitive protein detection, Biosens. Bioelectron. 54 (2014) 20–26. [14] C.-M. Wang, H. Cui, Electrogenerated chemiluminescence of luminol in neutral and alkaline aqueous solutions on a silver nanoparticle self-assembled gold electrode, Luminescence 22 (2007) 35–45. [15] J.-N. Shu, W. Wang, H. Cui, Direct electrochemiluminescence of gold nanoparticles bifunctionalized by luminol analogue-metal complexes in neutral and alkaline media, Chem. Commun. 51 (2015) 11366–11369. [16] X.-Q. Zhu, Q.-F. Zhai, W.-L. Gu, J. Li, E.-K. Wang, High-sensitivity electrochemiluminescence probe with molybdenum carbides as nanocarriers for α fetoprotein sensing, Anal. Chem. 89 (2017) 12108–12114.
3.4. Application of the ECL immunosensor for AFP detection in human plasma The applicability of the immunosensor was investigated by detecting AFP in human plasma. Different known concentrations (0.01, 0.1 ng mL−1) of AFP were added to clinical plasma samples, then the samples were diluted 10 times with 0.01 M PBS buffer (pH = 7.4). As shown in Table S2, the AFP immunosensor has good detection recovery. Thus the constructed immunosensor could be applied to the detection of AFP in human serum samples.
4. Conclusions In summary, a label-free ECL immunosensor based on ultrathin Co/ Ni-MOF nanosheet structure and luminol-AgNPs has been successfully constructed. The nanosheet and microflower-like assembly structure of the Co/Ni-MOF has greatly improved the ECL performance of the luminol-AgNPs system, attributed to their large surface area, resistance to particle agglomeration and the high catalytic activity of the Co/NiMOF. The prepared ECL immunosensor has been applied to detect the tumor marker AFP, with great sensitivity, selectivity and stability, and the immunosensor can be used for the determination of AFP in human serum samples. The sensitivity of this sensor for AFP was about 0.417 pg mL−1, comparable with that obtained by 2D bilayer structures based on graphene and graphene oxides for TNT [19], but was not as high as that made from pure cobalt MOF, which may be due to that the catalytic activity of Co ion is higher than that of Ni ion toward the reaction of luminol ECL. But the stability for the Co/Ni-MOF based sensor was a little better than that of Co based MOF. This report is a good demonstration of the application of MOF micro/nano structures for high-performance ECL immunosensors.
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Shanshan Wang is a MS student in College of Chemistry, Liaoning University, and joint training in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Her current research interests mainly focus on electrochemiluminescence sensors. Minmin Wang is a PhD student in the University of Science and Technology of China. Her research focuses on electrocatalyst. Chuanping Li is a PhD student in the University of Science and Technology of China. His main research interest focuses on plasmonic nanostructures and electrocatalyst. Haijuan Li is an assistant researcher in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Her research focuses on electrochemical sensors. Chunhua Ge is professor in College of Chemistry, Liaoning University. His current research interests mainly focus on the supramolecular assembly and synthesis of organic and organic-inorganic hybrid materials. Xiangdong Zhang is professor in College of Chemistry, Liaoning University. His current main research direction is the construction and application of boron and carbon functional hybrid materials. Yongdong Jin is professor of Chemistry at the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His research interests include plasmonic nanostructures, nanomedicine, energy/nano interface and catalysis, and nanopore-based analytics.
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A highly sensitive and stable electrochemiluminescence immunosensor for alpha-fetoprotein detection based on luminol-AgNPs@Co/Ni-MOF nanosheet microflowers
T
Shanshan Wanga,b, Minmin Wangb,c, Chuanping Lib,c, Haijuan Lib,*, Chunhua Gea,*, Xiangdong Zhanga, Yongdong Jinb,c,* a b c
College of Chemistry, Liaoning University, Shenyang 110036, China State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China University of Chinese Academy of Sciences, Beijing 100049, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Electrochemiluminescence Metal-organic framework Label-free immunosensor Alpha–fetoprotein
Due to their high catalytic effect on the electrochemiluminescence (ECL) of luminol, noble metal nanoparticles (NPs) have been widely used in luminol-based ECL immunosensors. However the aggregation of NPs often resulted in the decrease of ECL signal and affected the stability and durability of the sensor. In this study, a microflower-like structure made of ultrathin Co/Ni-based metal-organic frameworks (MOF) nanosheets were used as a platform for luminol-functionalized AgNPs to construct an immunosensor for tumor marker alphafetoprotein. The nanosheet and microflower-like assembly structure of the Co/Ni-MOF greatly improved the ECL performance of the luminol-AgNPs system, attributed to their large surface area, resistance to particle agglomeration and the high catalytic activity of the Co/Ni-MOF. The ultrathin Co/Ni-MOF was full of atomically dispersed cobalt ions and nickel ions, which can catalyze the ECL reaction of luminol and H2O2. The as-fabricated immunosensor has a good sensitivity with detection limit of 0.417 pg mL−1 (S/N=3), and shows satisfactory performance in practical applications.
1. Introduction Electrochemiluminescence (ECL), the combination of chemiluminescence and electrochemistry, possessing the advantage of both technologies, such as low background signals, wide dynamic range, high sensitivity, easy control and simple device, is a powerful tool in immunoassays and clinical diagnosis [1–11]. Due to its high luminous efficiency and low excitation potential, luminol is one of the most widely used ECL reagents. And as luminol is a reducing reagent, it has been frequently used to synthesize luminol-functionalized noble metal NPs. These NPs have a high catalytic effect on luminol ECL reactions. In addition to noble metal NPs, metal ions are also used to enhance the ECL intensity of luminol as they can catalyze the reaction between luminol and H2O2 [12–14]. For example, Cui et al. synthesized gold NPs bifunctionalized by luminol and Co2+-based metal complexes [15], in which the introduction of Co2+ complexes greatly enhanced the ECL of luminol-AuNPs. Although noble metal NPs possess high catalytic effect on luminol ECL, the aggregation/agglomeration of NPs in the electrochemical
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process often influences the long stability of ECL sensors. To prevent the agglomeration of NPs and to further improve the ECL behavior, nanomaterials with large surface area and catalytic properties were used as platforms to support luminol-AuNPs, such as molybdenum carbides [16], ZnO [17], graphite-like carbon nitride [18], graphene [19] etc. Cui et al. constructed a label-free aptasensor for TNT based on 2D bilayer structure of luminescence and catalytic functionalized graphene and graphene oxides [19]. The aptasensor has a low detection limit of 0.63 pg mL−1 for TNT, but the construction procedure was a bit complicated, in which N-(aminobutyl)-N-(ethylisoluminol)/hemin dualfunctionalized graphene hybrids and luminol functionalized silver/ graphene oxide composite were both employed. MOFs represent a diversity of highly porous materials wherein metal cations are connected by organic linkers [20–24]. Attributed to their abundant porosity and large internal surface areas, MOFs are widely used in areas of gas storage, separation, catalysis, and recently in ECL detections. For example, Yuan et al. synthesized a novel mesoporous luminescence-functionalized MOF (Ru–PCN-777) with high stability and excellent ECL performance, and constructed it into an
Corresponding authors. E-mail addresses: [email protected] (H. Li), [email protected] (C. Ge), [email protected] (Y. Jin).
https://doi.org/10.1016/j.snb.2020.127919 Received 31 October 2019; Received in revised form 16 February 2020; Accepted 24 February 2020 Available online 26 February 2020 0925-4005/ © 2020 Elsevier B.V. All rights reserved.
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were purchased from Shanghai Linc-Bio Science Co. LTD (Shanghai, China) while other proteins such as D-biotin, immunoglobulin G (IgG), bovine serum albumin (BSA) and myoglobin (Mb) were obtained from Sinopharm Chemical Reagent Co. Ltd. (Beijing, China). The H2O2 solution were freshly prepared from 30 % H2O2 (Xinke Electrochemical Reagent Factory, Bengbu, China) for daily use. Water was purified with a Millipore system and 0.1 M phosphate buffered saline (PBS) with pH of 7.4 was used for incubation. All of other reagents were of analytical grade.
immunosensor for mucin 1 detection [22]. Shao et al. developed a onestep strategy for fabrication of tris (bipyridine) ruthenium (II)-functionalized MOF (Ru-MOF) thin films using a self-assembly approach assisted by an electrochemical way. The Ru-MOF modified electrode was used to detect human heart-type fatty-acid-binding protein with great selectivity and stability [23]. Our group developed a ZIF-67 enhanced label-free ECL immunosensor for cardiac troponin I, the introduction of Co-based MOF greatly enhanced the sensitivity of the immunosensor [24]. As an oncofetal glycoprotein, alpha fetoprotein (AFP) has a low concentration in normal adult serum, and when it exceeded 20 ng mL−1, it is an early indicator of Hepatocellular carcinoma. Being one of the most important tumor marker for liver cancer, researchers have endeavored much effort in detecting AFP. Due to its high sensitivity and selectivity, simple equipment and low cost, immunoassays based on ECL and electrochemistry have attracted more and more attention. For example, Luo and coworkers developed recently a novel label-free electrochemical immunosensor for AFP based on oxygen reduction reaction [25]. In their study, rhombic dodecahedral Cu3Pt nanoframe was used as a high efficient catalyst for oxygen reduction reaction, which acts as a signal amplification platform for the immunosensor and guarantees its high sensitivity. In this study, a microflower-like structure made of ultrathin Co/NiMOF nanosheets and luminol-functionalized AgNPs was used as a superior ECL platform for immunosensor (Scheme 1). The microflowerlike assembly structure of the Co/Ni-MOF nanosheet has greatly improved the ECL performance of the luminol-AgNPs system, due to their large surface area, resistance to particle agglomeration and the high catalytic activity. Furthermore, the micro-/nano-structured composites of luminol-AgNPs@Co/Ni-MOF were used to construct a label-free immunosensor for AFP. The as-fabricated immunosensor has a low detection limit (0.417 pg mL−1, S/N = 3) towards AFP and a wide linear range from 1 pg mL−1 to 100 ng mL−1. The sensor has a good selectivity and showed satisfactory performance in serum sample detections.
2.2. Synthesis of luminol-AgNPs Luminol-functionalized AgNPs (luminol-AgNPs) were synthesized according to the previous reports [26,27]. The procedures were as follows: firstly, 3 mL of 5 mM AgNO3 was added to a solution containing 5 mL of ultrapure water and 9 mL of absolute ethanol and stirred vigorously. Then, 0.5 mL of 0.01 M luminol in 0.1 M NaOH was added to the mixture as soon as possible to get a yellow solution. All these procedures were conducted at room temperature and kept stirring continuously for 2 h with the color changed from light yellow to dark yellow, indicating the successful formation of luminol-AgNPs. Finally, after centrifugation at 10,000 rpm for 10 min, the soft sediment was obtained for further use. 2.3. Synthesis of ultrathin Co/Ni-MOF nanosheet microflowers The ultrathin Co/Ni-MOF was synthesized according to the following steps [28]. Briefly, 9 mmol of Co(NO3)2·6H2O and 1 mmol Ni (NO3)2·6H2O were dissolved in 30 mL of methanol to form solution A. Then, 3 mmol of 2-methylimidazole was dissolved in 10 mL of methanol to form solution B. The two solutions were mixed and stirred for 2 min, then kept static at room temperature for 24 h. After that the solution was centrifuged and washed by methane for three times. 2.4. Deposition of luminol-AgNPs on the surface of Co/Ni-MOFs As indicated in dynamic light scattering data (Figure S4), the surfaces of luminol-AgNPs and Co/Ni-MOF were oppositely charged, so luminol-AgNPs can be adsorbed on the surface of Co/Ni-MOF nanosheet microflowers by electrostatic interaction. The composites of luminol-AgNPs@Co/Ni-MOF were obtained by mixing luminol-AgNPs with Co/Ni-MOF and shook vigorously.
2. Experimental section 2.1. Chemical and reagents Luminol and AgNO3 were obtained from Sigma-Aldrich (Milwaukee, WI, USA). 2-methylimidazole (MeIM), Co(NO3)2 and Ni (NO3)2 were purchased from Aladdin. Both biotin-anti-AFP and AFP
2.5. Fabrication of the ECL immunosensor for AFP detection Before the fabrication, the gold electrode was polished with 1 μm and 0.3 μm alumina in turn. After ultrasonicated in ultra-pure water for 5 min and rinsed with ultra-pure water for several times, the electrode was dried with inert gas argon to get a mirror-like surface. Then the electrode was scanned in 1 M H2SO4 at a scan rate of 0.5 V/s in the potential range between -0.4 V and 1.6 V versus Ag/AgCl using cyclic voltammetry (CV) until a reproducible CV was obtained, and the electrode was rinsed with distilled water for further uses. Finally, the electrode was irradiated with a novascan PSD Pro series UV ozone cleaning system for 30 min prior to sensor construction. Next, the cleaned gold electrode was incubated in 1,3-propanedithiol solution overnight to obtain the Au-S bond. After rinsed with ethanol and ultrapure water, 2 μL of as-prepared luminol-AgNPs@Co/ Ni-MOF was dropped on the surface of the electrode. Then the electrode was dried at room temperature, and 2 μL of biotin-anti-AFP solution was dropped and incubated at 4 °C for 12 h. To block the remaining binding sites, 2 μL of 1 % BSA was placed onto the electrode. After rinsed with 0.1 M PBS buffer (pH = 7.4), the BSA/biotin-anti-AFP/ luminol-AgNPs@Co/Ni-MOF/1,3-propanedithiol/Au electrode was formed and stored at 4 °C for use.
Scheme 1. Sensing mechanism and the fabrication procedures of the microflower-like luminol-AgNPs@Co/Ni-MOF based immunosensor for the detection of AFP. 2
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(TEM) in Fig. 1. As seen from atomic force microscopy (AFM) measurement of the ultrathin Co/Ni-MOF nanosheets in Figure S1, the thicknesses of the Co/Ni-MOF nanosheets was as thin as ∼ 1 nm, which will facilitate catalytic reactions due to the existence of rich coordinative unsaturated metal sites on the surfaces. The specific surface area and pore diameter of the Co/Ni-MOF were measured by Brunauer Emmett Teller (BET) adsorption isotherm and Barrett–Joyner–Halenda (BJH) methods. As shown in Figure S2, the specific area and pore size distribution of the Co/Ni-MOF were obtained to be ∼ 97.25 m2/g and 3.75 nm, respectively, indicating a mesoporous structure. LuminolAgNPs were prepared according to previous report [26,27]. As shown in Figure S3, the diameter of the luminol-AgNPs was about 33 nm. Since the surface of Co/Ni-MOF nanosheets and luminol-AgNPs were oppositely charged (Figure S4), the luminol-AgNPs can easily decorate on the surface of Co/Ni-MOF nanosheets by electrostatic interactions. As shown in Fig. 1(C–I), luminol-AgNPs were uniformly dispersed on the surface of Co/Ni-MOF nanosheets. The successful adsorption of luminol-AgNPs on Co/Ni-MOF nanosheets was further confirmed by UV–vis spectrum and X-ray photoelectron spectra (XPS), respectively. As shown in Fig. 2, for pure luminol, characteristic UV–vis absorbance peaks were appeared at about 200 nm, 230 nm, 305 nm and 350 nm; while luminol-AgNPs showed absorbance peaks at 220 nm, 290 nm, 365 nm and 425 nm, the characteristic of luminol and AgNPs. The luminol-AgNPs@Co/Ni-MOF complex exhibited the characteristic absorbance peak of Co/Ni-MOF nanosheets at 215 nm and two peaks of luminol-AgNPs at 365 nm and 420 nm, respectively [26,27], indicating that luminol-AgNPs were successfully incorporated with Co/Ni-MOF nanosheets. The components and the elements valences of the Co/NiMOF nanosheets were further characterized by XPS measurements (Figure S5). The XPS peaks located at 781.35 eV and 873.15 eV were assigned to Co 2p and Ni 2p state in Co/Ni-MOF nanosheets. The Co 2p and Ni 2p spectra can be extended to 780.75 eV (Co2+ ions) and 796.5 eV (Co3+ ions), 855.6 eV (Ni2+ ions) and 873.15 eV (Ni3+ ions) respectively, indicating that both cobalt and nickel were present in the form of divalent state [28–30]. Compared with the XPS survey of Co/ Ni-MOF, two new peaks located at 368.08 eV and 374.08 eV caused by Ag 3d [31] were observed in the XPS survey of luminol-AgNPs@Co/NiMOF, indicating that the luminol-AgNPs were successfully confined on the surface of Co/Ni-MOF nanosheets. Moreover, the present of Ag
2.6. ECL detection of AFP with the immunosensor A certain concentration of AFP was dropped on the surface of modified gold electrode and incubated for about 30 min. After dried at room temperature, the electrode was rinsed by 0.1 M PBS buffer (pH = 7.4) to remove the excess AFP. Then the modified gold electrode was used as the working electrode for ECL detection, Ag/AgCl (saturated KCl) electrode was connected as the reference electrode, and Pt wire was used as counter electrode. Using the three-electrode system, the ECL experiments were conducted with CV scanning from -1.3 to 1.3 V, the prepared immunosensor was placed in an ECL detector cell containing 700 μL of H2O2 in 0.1 M PBS (pH = 9) to measure the ECL intensity of the sensor. 2.7. Characterizations Transmission electron microscopy (TEM) images were obtained using a Hitachi 600 transmission electron microscope at an acceleration voltage of 100 kV (Hitachi, Tokyo, Japan). X-ray photoelectron spectroscopy (XPS) measurements were performed on an Escalab 250Xi, Thermo Fisher Scientific. Scanning electron microscope (SEM) images were obtained using XL30 ESEM FEG SEM (Philips, Netherlands). UV–vis absorption spectra were performed using a Lambda 750 spectrophotometer (Perkin-Elmer). The Zeta potential values of Co/Ni-MOF and luminol-AgNPs were taken from the Zeta sizer Nano-Z system (Malveren Instruments). The cyclic voltammetry of the electrode was conducted by an electrochemical workstation (CHI660E, Chenhua, Shanghai), and the ECL signal of the electrode was obtained by MPI-A capillary electrophoresis ECL system (Xi'an Ruimai Electronics Co., Ltd., Xi'an, China). 3. Results and discussions 3.1. Characterization of the luminol-AgNPs@Co/Ni-MOF complex First, the ultrathin Co/Ni-MOF nanosheets were prepared by the method mentioned before [28]. The obtained Co/Ni-MOF nanosheets showed a flower-like layered assembly structure as seen from scanning electron microscopy (SEM) and transmission electron microscopy
Fig. 1. Overall and partially enlarged SEM images (A) and typical TEM images of the as-prepared microflower-like Co/Ni-MOF (B). Typical TEM images of luminolAgNPs@Co/Ni-MOF (C). TEM images and elemental mapping analyses of a single luminol-AgNPs@Co/Ni-MOF particle (D-I). 3
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Fig. 2. UV/Vis absorption spectra of luminol-AgNPs (a), Co/Ni-MOF (b), luminol-AgNPs@Co/Ni-MOF (c) and luminol (d).
Fig. 4. Effect of the ratio (A) of Co/Ni-MOF to luminol-AgNPs on ECL intensity in 0.1 M PBS (pH = 7.4) containing 0.1 mM H2O2. Photomultiplier tube: 800 V. Effect of pH value (B) of the solution with 0.1 M PBS containing H2O2. Photomultiplier tube: 500 V.
enhancement. Most importantly, the ultrathin nanosheets and microflower-like assembly structure were good platform for supporting luminol-AgNPs, which effectively prevent the agglomeration of luminolAgNPs during electrochemical process. Moreover, the atomically dispersed Co and Ni ions in the MOF structure can facilitate the catalysis reaction between luminol and H2O2. The high catalytic effect of Co/NiMOF was further confirmed by CVs on the luminol-AgNPs modified electrode. As shown in Fig. 3B, for the luminol-AgNPs modified electrode, there were mainly three groups of redox peaks; the oxidization peak at ∼ 0.4 V and redox peaks at ∼ 0.2 V and 0.1 V were caused by the oxidation and reduction of AgNPs [31]. The redox peak at about -0.3 V to -0.4 V was observed which was attributed to the reduction of H2O2 and O2; this peak was decreased at N2 saturated atmosphere, confirmed that O2 was also reduced at the cathode electrode (Figure S10). The redox peak at around 1.0 V can be ascribed to oxidation and reduction of the gold electrode. After combined with Co/Ni-MOF nanosheets, the redox peaks of AgNPs were covered by Co/Ni-MOF, but the reduction of H2O2 and O2 was enhanced a lot which indicated that the integration of Co/Ni-MOF catalyzed the reduction of H2O2 and O2; while the redox of gold electrode was greatly enhanced and a new reduction peak at around -1.0 V was appeared which can be ascribed to the H2 evolution catalyzed by Co/Ni-MOF nanosheets. The ECL reached its highest intensity at ∼ 0.5 V (Fig. 3A), which is consistence with the electrocatalytic oxidation of luminol [32]. Besides H2O2, O2 is also an important coreactant of luminol ECL [15,32]; the dissolved oxygen and H2O2 were reduced to OOH− at about −0.4 V, while during the reverse scan, OOH− was electro-oxidized to O2%‾, which reacts with the luminol anion to produce excited-state species, and emits light.
Fig. 3. ECL intensity-potential curves (A) and cyclic voltammograms (B) of luminol-AgNPs@Co/Ni-MOF and luminol-AgNPs in the solution of 0.1 M PBS (pH = 7.4) containing 0.1 mM H2O2.
element in the quantitative assessment (Figure S7&S8) also confirmed the successful attachment of luminol-AgNPs on the surface of Co/NiMOF nanosheets.
3.2. CV and ECL behavior of the luminol-AgNPs@Co/Ni-MOF complex As shown in Fig. 3A, the ECL intensity of luminol-AgNPs@Co/NiMOF complex was about 3 times higher than that of luminol-AgNPs alone in the same condition. In order to investigate the enhancement mechanism of the Co/Ni-MOF on the ECL of luminol, the ECL behavior of the luminol-AgNPs modified gold electrode was studied in the presence of free Co2+ and Ni2+ with same content of that in Co/Ni-MOF (obtained by ICP MS) in the electrolyte solution. The electrode showed ∼ 1.69 times enhancement on the ECL intensity (Figure S9), which indicated that the structure of the Co/Ni-MOF affected a lot on the ECL
3.3. ECL detection of AFP To demonstrate sensing applicability of the luminol-AgNPs@Co/Ni4
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Fig. 6. ECL responses (A) and corresponding calibration curve (B) of ECL intensity to the logarithmic AFP concentration in 0.1 M PBS (pH = 9) buffer containing 0.1 mM H2O2.
Fig. 5. CV characterizations (A) in 0.1 M KCl containing 5.0 mM K3Fe(CN)6 aqueous solution and ECL responses (B) in 0.1 M PBS solution (pH = 9) containing 0.1 mM H2O2 for each modification step on gold electrode: (a) gold electrode/ 1,3-propanedithiol, (b) gold electrode/ 1,3-propanedithiol/ luminolAgNPs@Co/Ni-MOF, (c) gold electrode/ 1,3-propanedithiol/ luminolAgNPs@Co/Ni-MOF/ biotin-anti-AFP, (d) gold electrode/ 1,3-propanedithiol/ luminol-AgNPs@Co/Ni-MOF/ biotin-anti-AFP/ BSA, (e) gold electrode / 1,3propanedithiol / luminol-AgNPs@Co / Ni-MOF / biotin-anti-AFP / BSA/AFP, (f) bare gold electrode.
MOF, a label-free immunosensor was built to detect AFP. Before the construction of the immunosensor, the ratio of Co/Ni-MOF to luminolAgNPs and the pH of the solution were optimized. As shown in Fig. 4, the ratio of Co/Ni-MOF to luminol-AgNPs was adjusted from 0.3:1 to 2:1, the ECL intensity reach the highest at the ratio of 0.5:1. This may be caused by poor conductivity of the MOF which will decrease ECL intensity after the ratio higher than 0.5:1 [33,34]. It has been reported that the pH of ECL solution affects a lot on the ECL reaction [35–37]; suitable concentrations of OH− is helpful to generate O2%‾, so for most of luminol ECL, optimal reaction conditions occur under alkaline conditions. In this study, the pH of solution was adjusted from 7 to 10 and the highest ECL intensity was achieved at the pH of 9, which is accordance to the previous reports [36]. So, the ratio of Co/Ni-MOF to luminol-AgNPs as 0.5:1 and the pH 9 of the solution were chosen for the further ECL experiments. After optimizing the detection conditions, the label-free AFP immunosensor was constructed and the procedures were depicted in Scheme 1. Briefly, 1,3-propanedithiol was first used to connect luminolAgNPs@Co/Ni-MOF to the Au electrode, biotin-anti-AFP was linked to AgNPs via the formation of Ag-S bond. After that, BSA was used to block the residual nonspecific binding sites [37]. The modification procedure was monitored by CVs scanned in 0.1 M KCl solution containing 5 mM K3Fe(CN)6. As shown in Fig. 5A, the redox peak current was decreased rapidly after the modification of 1,3-propanedithiol on Au electrode surface, due to the retardation of electron transfer by 1,3propanedithiol. After the modification of luminol-AgNPs@Co/Ni-MOF, new peaks appeared at ∼ 0.1 V and -0.05 V which is related to the redox of luminol-AgNPs [31,38]. After incubated successively with
Fig. 7. (A) Selectivity of the AFP ECL immunosensor measured at pH 9. The concentrations of D-biotin, Mb and IgG were 10 ng mL−1, while the concentration of AFP was 1 ng mL−1. The mixture contains all the above proteins. (B) Stability of the immunosensor toward 10 ng mL−1 AFP based on continuous cyclic scanning in 0.1 M PBS (pH = 9) solution containing 0.1 mM H2O2.
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Declaration of Competing Interest
biotin-anti-AFP, BSA and AFP, the proteins blocked the electron transfer of the electrode which made the current density decreased gradually in 0.1 M PBS (pH = 7.4), as shown in Figure S11. In addition to CV characterizations, the ECL intensity variation of each modification step of electrodes was also monitored. As shown in Fig. 5B, bare gold electrode and the 1,3-propanedithiol modified gold electrode exhibited no ECL response, while after modified with the luminolAgNPs@Co/Ni-MOF, there was a prominent ECL peak. After the incubation with biotin-anti-AFP, BSA and AFP, the ECL intensity decreased in succession due to the blocking of electron transfer by the proteins as confirmed by CV characterizations. Based on the drop in ECL signal in the presence of AFP, we can calculate the concentration of AFP. As shown in Fig. 6, with the concentration of AFP increased from 1 pg mL−1 to 100 ng mL−1, the ECL intensity of the immunosensor decreased correspondingly. The regression equation was I = 821.41lgc – 5385.8 and the correlation coefficient was 0.988, where I was ECL intensity and c was the concentration of AFP (g/mL) [16]. The detection limit was 0.417 pg mL−1 at a signal-to-noise ratio of 3 (S/ N = 3). We have compared that with other reported methods in Table S1; the sensor based on our method is comparable with other methods and previous ECL methods. Three interfering proteins (IgG, Mb, Dbiotin) were further chosen to check the selectivity of the immunosensor. The concentration of IgG, Mb, D-biotin were all 10 ng mL−1, and the concentration of AFP was chosen as 1 ng mL−1. As shown in Fig. 7A, the ECL intensity decreased only in the presence of AFP and the mixture containing AFP, indicating good selectivity of the immunosensor. Fig. 7B shows the stability test of the as-prepared immunosensor with 10 ng mL−1 AFP in 0.1 M PBS (pH = 9) buffer containing 0.1 mM H2O2, the relative standard deviation (RSD) was 1.25 %, manifesting the good stability of the constructed immunosensor.
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. CRediT authorship contribution statement Shanshan Wang: Methodology, Writing - original draft. Minmin Wang: Methodology, Data curation. Chuanping Li: Data curation. Haijuan Li: Conceptualization, Writing - review & editing. Chunhua Ge: Supervision. Xiangdong Zhang: Supervision. Yongdong Jin: Conceptualization, Writing - review & editing, Supervision, Funding acquisition, Project administration. Acknowledgments This work was supported by the National Key Research and Development Program of China Grant No. 2016YFA0201300, the National Natural Science Foundation of China grant Nos. 21675146 and 21475125), and the Instrument Developing Project of the Chinese Academy of Sciences (Grant No. YZ201666). We are pleased to acknowledge the generous support of ECL instrument by Prof. Guobao Xu. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.snb.2020.127919. References [1] M.M. Richter, Electrochemiluminescence (ECL), Chem. Rev. 104 (2004) 3003–3036. [2] L.-Z. Hu, G.-B. Xu, Applications and trends in electrochemiluminescence, Chem. Soc. Rev. 39 (2010) 3275–3304. [3] K. Muzyka, M. Saqib, Z.-Y. Liu, W. Zhang, G.-B. Xu, Progress and challenges in electrochemiluminescent aptasensors, Biosens. Bioelectron. 92 (2017) 241–258. [4] Z.-Y. Liu, W.-J. Qi, G.-B. Xu, Recent advances in electrochemiluminescence, Chem. Soc. Rev. 44 (2015) 3117–3142. [5] L. Cui, J. Wu, H.-X. Ju, Electrochemical sensing of heavy metal ions with inorganic, organic and bio-materials, Biosens. Bioelectron. 63 (2015) 276–286. [6] S.-Y. Deng, H.-X. Ju, Electrogenerated chemiluminescence of nanomaterials for bioanalysis, Analyst 138 (2013) 43–61. [7] S.-J. Xu, Y. Liu, T.-H. Wang, J.-H. Li, Positive potential operation of a cathodic electrogenerated chemiluminescence immunosensor based on luminol and graphene for cancer biomarker detection, Anal. Chem. 83 (2011) 3817–3823. [8] H.-R. Zhang, M.-S. Wu, J.-J. Xu, H.-Y. Chen, Signal-on dual-potential electrochemiluminescence based on luminol-gold bifunctional nanoparticles for telomerase detection, Anal. Chem. 86 (2014) 3834–3840. [9] A. Karsten, F.M. Pravda, G.G. Guilbault, Recent applications of electrogenerated chemiluminescence in chemical analysis, Talanta 54 (2001) 531–559. [10] H.-M. Wang, C.-C. Wang, A.-J. Wang, L. Zhang, X.-L. Luo, P.-X. Yuan, J.-J. Feng, Green synthesis of Pd nanocones as a novel and effective electrochemiluminescence illuminant for highly sensitive detection of dopamine, Sens. Actuators B Chem. 281 (2019) 588–594. [11] H.-M. Wang, Y. Fang, P.-X. Yuan, A.-J. Wang, X.-L. Luo, J.-J. Feng, Construction of ultrasensitive label-free aptasensor for thrombin detection using palladium nanocones boosted electrochemiluminescence system, Electrochim. Acta 310 (2019) 195–202. [12] X.-B. Feng, N. Gan, H.-R. Zhang, Q. Yan, T.-H. Li, Y.-T. Cao, F.-T. Hu, H.-W. Yu, Q.L. Jiang, A novel “dual-potential” electrochemiluminescence aptasensor array using CdS quantum dots and luminol-gold nanoparticles as labels for simultaneous detection of malachite green and chloramphenicol, Biosens. Bioelectron. 74 (2015) 587–593. [13] X.-Y. Jiang, Y.-Q. Chai, H.-J. Wang, R. Yuan, Electrochemiluminescence of luminol enhanced by the synergetic catalysis of hemin and silver nanoparticles for sensitive protein detection, Biosens. Bioelectron. 54 (2014) 20–26. [14] C.-M. Wang, H. Cui, Electrogenerated chemiluminescence of luminol in neutral and alkaline aqueous solutions on a silver nanoparticle self-assembled gold electrode, Luminescence 22 (2007) 35–45. [15] J.-N. Shu, W. Wang, H. Cui, Direct electrochemiluminescence of gold nanoparticles bifunctionalized by luminol analogue-metal complexes in neutral and alkaline media, Chem. Commun. 51 (2015) 11366–11369. [16] X.-Q. Zhu, Q.-F. Zhai, W.-L. Gu, J. Li, E.-K. Wang, High-sensitivity electrochemiluminescence probe with molybdenum carbides as nanocarriers for α fetoprotein sensing, Anal. Chem. 89 (2017) 12108–12114.
3.4. Application of the ECL immunosensor for AFP detection in human plasma The applicability of the immunosensor was investigated by detecting AFP in human plasma. Different known concentrations (0.01, 0.1 ng mL−1) of AFP were added to clinical plasma samples, then the samples were diluted 10 times with 0.01 M PBS buffer (pH = 7.4). As shown in Table S2, the AFP immunosensor has good detection recovery. Thus the constructed immunosensor could be applied to the detection of AFP in human serum samples.
4. Conclusions In summary, a label-free ECL immunosensor based on ultrathin Co/ Ni-MOF nanosheet structure and luminol-AgNPs has been successfully constructed. The nanosheet and microflower-like assembly structure of the Co/Ni-MOF has greatly improved the ECL performance of the luminol-AgNPs system, attributed to their large surface area, resistance to particle agglomeration and the high catalytic activity of the Co/NiMOF. The prepared ECL immunosensor has been applied to detect the tumor marker AFP, with great sensitivity, selectivity and stability, and the immunosensor can be used for the determination of AFP in human serum samples. The sensitivity of this sensor for AFP was about 0.417 pg mL−1, comparable with that obtained by 2D bilayer structures based on graphene and graphene oxides for TNT [19], but was not as high as that made from pure cobalt MOF, which may be due to that the catalytic activity of Co ion is higher than that of Ni ion toward the reaction of luminol ECL. But the stability for the Co/Ni-MOF based sensor was a little better than that of Co based MOF. This report is a good demonstration of the application of MOF micro/nano structures for high-performance ECL immunosensors.
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Shanshan Wang is a MS student in College of Chemistry, Liaoning University, and joint training in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Her current research interests mainly focus on electrochemiluminescence sensors. Minmin Wang is a PhD student in the University of Science and Technology of China. Her research focuses on electrocatalyst. Chuanping Li is a PhD student in the University of Science and Technology of China. His main research interest focuses on plasmonic nanostructures and electrocatalyst. Haijuan Li is an assistant researcher in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Her research focuses on electrochemical sensors. Chunhua Ge is professor in College of Chemistry, Liaoning University. His current research interests mainly focus on the supramolecular assembly and synthesis of organic and organic-inorganic hybrid materials. Xiangdong Zhang is professor in College of Chemistry, Liaoning University. His current main research direction is the construction and application of boron and carbon functional hybrid materials. Yongdong Jin is professor of Chemistry at the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His research interests include plasmonic nanostructures, nanomedicine, energy/nano interface and catalysis, and nanopore-based analytics.
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