Cerium Dioxide-Mediated Signal âOnâOffâ by Resonance Energy

Subscriber access provided by - Access paid by the | UCSB Libraries

Article

Cerium Dioxide Mediated Signal ‘on-off’ by Resonance Energy Transfer on Lab-on-paper Device for Ultrasensitive Detection of Lead Ion Yuzhen Huang, Li Li, Yan Zhang, Lina Zhang, Shenguang Ge, Hao Li, and Jinghua Yu ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.7b10629 • Publication Date (Web): 05 Sep 2017 Downloaded from http://pubs.acs.org on September 5, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

ACS Applied Materials & Interfaces is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Applied Materials & Interfaces

Cerium Dioxide Mediated Signal ‘on-off’ by Resonance Energy Transfer on Lab-on-paper Device for Ultrasensitive Detection of Lead Ion

Yuzhen Huang,#,† Li Li,#,† Yan Zhang,† Lina Zhang,‡ Shenguang Ge,*,† Hao Li,† Jinghua Yu†,§

†

Institute for Advanced Interdisciplinary Research, University of Jinan, Jinan 250022,

P.R. China ‡

Shandong Provincial Key Laboratory of Preparation and Measurement of Building

Materials, University of Jinan, Jinan 250022, P.R. China §

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022,

P.R. China #

These authors contributed equallly to this work.

*Corresponding author: Shenguang Ge E-mail: [email protected] Telephone: +86-531-82767161

ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ABSTRACT: In this report, a 3D microfluidic lab-on-paper device for ultrasensitive detection of lead cation was designed using phoenix tree fruit-shaped CeO2 nanoparticles (PFCeO2 NPs) as catalyst and 50 nm Ag NPs as quencher. Firstly, snowflake-like Ag NPs were grown on the paper working electrode through in-situ growth method and used as matrix for DNAzymes that were specific for Pb2+. After the addition of Ag NPs-labeled substrate strands, Ag NPs restrained the electrochemiluminescence (ECL) intensity of luminol greatly through resonance energy transfer from luminol to Ag NPs. However, under the existence of Pb2+, the substrate strands were seperated and then PFCeO2 NPs-labeled signal strands were hybridized with the DNAzymes. The ECL signal got improved greatly under the fast catalytic reaction between PFCeO2 NPs and H2O2, which converted the response from signal off to signal on state, resulting in sensitive detection of Pb2+. Under the optimal conditions, ECL signal response exhibited a good linear relationship with the logarithm of lead cation in a wide linear range from 0.05 to 2000 nM and an ultralow detection limit of 0.016 nM. Meanwhile, such sensor featured with good specificity, acceptable stability, reproducibility and low-cost, provides a promising portable, simple and effective strategy for Pb2+ detection. KEYWORDS: Cerium dioxide, Resonance energy transfer, Signal ‘on-off’, Lab-on-paper, Lead ion


Page 2 of 30

Page 3 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1. INTRODUCTION Recently, water contamination issue, especially lead ions (Pb2+) water pollution, has attracted more attention among all circles of the society because long-term excessive absorption of high-level Pb2+ will initiate many diseases, such as cancers of the lung and sinus cavity.1-2 Therefore, it is urgent to explore novel methods to sensitive detection of Pb2+. Up to now, although great progress in the development of various sensors,

including

fluorescence

sensors,3-4

colorimetric

sensors,

5-7

electrochemiluminescence (ECL) sensors, have been made. Major technological challenges still remain such as qualitative or semi-quantitative measurement with unaccurate results in colorimetric detection. Fluorescence sensors exhibit high sensitivity and selectivity, but fluorescence analytical method is limited by valuable equipments and highly trained personnel. ECL method assembling advantages of chemiluminescent technology and electrochemical analysis,8-12 have been identified with simplified set-up, high reproducibility, controllability and sensitivity,13-17 which may be one potential analytical method to realize on-site detection of Pb2+. The increasing demands of biological and environmental assays accelerate the development of versatile detection devices for sensitive detection of disease-related proteins and pollutants. Paper, since first reported by Whitesides group,18 has been gaining more and more attention owing to its attractive features including inexpensive, abundant, ease of use, store, portability and excellent chemical compatibility. Various reliable paper-based devices19-21 have been made in our group, including antigen-antibody, hydrogen sulphide,22 aptamer,23 cell,24 H2O225 and so on.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Specially, paper has been used as a simple and sensitive platform for metal ions detection in recent years because of its easy miniaturized, convenient signal quantification and portable, which is well-suited for providing rapid and reproducible quantitative results without the need for personnel in a specific field.26-29 In order to ensure the sensitivity of determined result for the lab-on-paper device, signal amplification strategies have to be adopted. Nanomaterials are widely used as signal amplifiers in biosensor owing to their unique electrical, optical, and thermal properties.30-32 In particular, silver nanoparticles (NPs) have the features of low-cost, highly conductive, easily synthesized and controllable morphology, which can be used as excellent sensor carrier to carry biomolecule.33-36 In this work, two kinds of morphology Ag NPs were synthesized and used as different carriers. Snowflake-like Ag NPs (SLAg NPs) were first prepared and grown on the paper work electrode (PWE) in situ through a simple chemical reduction and then were used as ideal nanocarriers for DNAzymes (S1) by Ag-S bond. The ECL signal of luminol was significantly enhanced due to the features of huge active area and fast electron transfer rate of SLAg NPs-PWE. Besides, 50 nm Ag NPs were used as quencher to modify substrate strands (S2) through resonance energy transfer (RET) between luminol and 50 nm Ag NPs. After adding Pb2+ in the paper working electrode, the S2 was cleaved, and then phoenix tree fruit-like CeO2 (PFCeO2 NPs)-labeled signal strand (S3) was hybridized with S1. The ECL intensity was recovered greatly under the super catalytic action of PFCeO2 NPs toward coreactant H2O2, which produced numerous reactive oxygen species (ROSs) and thus enhancing the luminous efficiency of luminol. In


Page 4 of 30

Page 5 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


view of its advantages, combining PFCeO2 NPs with 50 nm Ag NPs as enhancer and quencher respectively is a simple yet a practical method for developing an ultrasensitive ECL sensor to quantitative Pb2+. Herein, a prototype of a new type of 3D ECL lab-on-paper device (ECL-LPD) for ultrasensitive and specific detection of Pb2+ was first designed by using SLAg NPs-PWE as biosensor substrate and PFCeO2 NPs as enhancer of the ECL signal. After Ag NPs-labeled S2 hybridized with S1, the ECL intensity was reduced via RET process, which made the ECL responds in “signal off” state. On the other hand, with Pb2+ added into the electrolyte, PFCeO2 NPs-labeled S3 with excellent electro-catalytic activity toward H2O2 was connected to the electrode through hybridization between S1 and S3. This process recovered the ECL of luminol molecules, and thus the ECL response is transformed into “signal on” state, resulting in ultrasensitive detection of Pb2+ with detection limit of 0.016 nM. This work demonstrated here provided a promising and general way for on-site, portable, simple and sensitive detection of Pb2+ in the environment monitoring applications. 2. EXPERIMENTAL SECTION 2.1. Materials. The synthetic oligonucleotides were purchased from Sangon Biotech Co., Ltd. (Jinan, China). The sequence information is shown in Table S1. Silver nitrate (AgNO3) was received from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China).

Tris

(2-carboxyethyl)

phosphine

hydro-chloride

(TCEP),

poly

(vinypyrrolidone) (PVP, MW~58000), ethylene glycol (EG), luminol (98%) and hydroxylamine (NH2OH, 50%, w/v) were bought from Sigma-Aldrich Co. (St. Louis,



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

MO, USA). Cerium trichloride (CeCl3·7H2O) was ordered from Shanghai Macklin Biochemical Co., Ltd. (Shanghai, China). H2O2 (30%, w/v) was acquired from Sigma-Aldrich Chemical Co. All the other chemicals were of analytical reagent grade and were used as received without further purification. All the solutions were prepared with double-distilled water purified by Lichun water purification system (≥18.25 MΩ cm，Jinan, China). 2.2. Instruments. Scanning electron microscope (SEM) images were performed using a JSM-6700F microscope (Japan) and used to characterize the materials. Transmission electron microscopy (TEM) images were tested on a Hitachi H-800 microscope (Japan). Electrochemical measurements were done using a CHI 660D electrochemical workstation (Shanghai CH Instruments Co., China). The electrochemical impedance spectroscopy (EIS) of the modified paper electrode were obtained from an IM6x electrochemical station (Zahner, Germany) to describe the impedance changes during the electrode modified process. The ECL measurements were carried out on a MPI-E multifunctional electrochemical and chemiluminescence analytical system (Xi’an Remax Analytical Instrument Ltd. Co.) biased at 800 V. 2.3. Preparation of SLAg NPs-PWE. This novel SLAg NPs-PWE with remarkably high accessible surface area and fast electron transfer rate was fabricated through a simple chemical reduction with appropriate modifications. 37 Firstly, 10 µL of 0.4 M AgNO3 aqueous solution was added into paper sample zone of the device. And then 40 µL of 1.6 M NH2OH was added quickly, followed by washing with ultrapure water to flush out the free Ag NPs. After that the device was naturally dried at room


Page 6 of 30

Page 7 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


temperature. Finally, our expected SLAg NPs-PWE was obtained successfully. 2.4. Synthesis of Ag NPs. Ag NPs were prepared according to the previous literature with some revision. 38 Briefly, a round bottom flask with three flask containing 5 mL of EG was heated at 160 °C for 1 h with vigorous stirring. 0.04 g of AgNO3 and 1.55 g of PVP were dispersed in 6 mL of EG quickly. Herein EG was served as both solvent and reductant. Subsequently, the mixture was added dropwise into the hot EG at the same time under vigorous stirring. Afterwards, the mixture was heated at 160 °C for another 45 min. Finally, the product was washed with alcohol for three times and collected by centrifugation. The synthesized material was kept in a dark place. 2.5. Preparation of PFCeO2 NPs. The PFCeO2 NPs were fabricated by a hydrothermal technique.39 0.1 g of CeCl3·7H2O and 0.5 g of PVP were dissolved in anhydrous ethanol in a beaker under vigorous stirring. Subsequently, 100 µL of formic acid and 200 µL of NH3·H2O were then added into the solution. The mixture was continuous stirring for 15 min to form a white colloidal solution. Subsequently, 100 µL of H2O2 (30%) was added and then the color of the solution turned to yellow. The mixture solution was transferred into 25 mL of Teflon-lined stainless steel autoclave. After heating in an oven at 150 °C for 6 h, the autoclave was cooled to room temperature naturally. Thereafter, thoroughly washed by deionized water and absolute ethanol four times, the product was dried at 70 °C under air atmosphere for 10 h. 2.6. Preparation of Ag NPs-labeled S2 and PFCeO2 NPs-labeled S3. The Ag NPs-labeled S2 was prepared as follows: First, the S2 was activated with 1.5 µL of 10



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

mM TCEP for 1 h. Then, 300 µL of re-dispersed Ag NPs solution was added, and then the mixture was shaken gently for 2 h. Excessive reagents were washed with deionized water for three times at 8000 rpm. Finally, the Ag NPs-labeled S2 was dispersed in a Tris–HCl buffer (pH 7.4) and stored at 4 °C. Preparation of PFCeO2 NPs-labeled S3: Firstly, S3 was activated with 1.5 µL of 10 mM TCEP in acetate buffer (pH 5.2) and incubated at room temperature for 1 h. Then, 300 µL of as-prepared PFCeO2 NPs was added into the mixture for incubating about 6 h under shaking. After that, for sealing the remaining active sites, 100 µL of 1 % 6-mercapto-1-hexanol (MCH) solution was dropped into the solution for another 1 h at room temperature. After that, excessive reagents were centrifugated and washed thoroughly with ultrapure water for several times. Thus, PFCeO2 NPs-labeled S3 was prepared. Finally, the composites were dissolved in Tris–HCl (10 mM, pH 7.4) buffer and stored at 4 °C for further use. 2.7. Preparation of the 3D ECL-LPD. The establishment process of the 3D ECL-LPD was similar as our previous work.40 The pattern for wax-printing was shown in Scheme 1A. The entire ECL-LPD was composed of two auxiliary tabs with the same size (15.0 × 25.0 mm) and one sample tab (20.0 × 25.0 mm). The sample tab (dark green) has three circular paper zones (6.0 mm in diameter) for screen-printed carbon counter electrode and working electrode as well as Ag/AgCl reference electrode. A reservoir was consisted of two auxiliary tads (the middle bright green layer and the bottom reseda layer) (as illustrated in Scheme 1B) .The middle white zone in bright green layer was hollow. The bottom reseda layer was half-hydrophilic


Page 8 of 30

Page 9 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


zone. The outer side was hydrophobic and the inside was hydrophilic (Scheme 1C). To explain the device clearly, the photos of the 3D ECL-LPD for each step were added into the supporting information (Figure S1). The electrochemical cell will form when the ECL-LPD was filled with buffer solution.

Scheme 1. The pattern for (A) wax-printing and (B and C) folding of the 3D ECL-LPD.

The detailed fabrication procedures of the ECL sensor were represented in Scheme 2. First, SLAg NPs-PWE was fabricated through a simple chemical reduction (Scheme 2B). And then, 10 µL of 1.0 mM S1 was dropped into the electrode and incubated at 4 °C for 6 h. The surface of the electrode was washed with Tris–HCl buffer (10 mM, pH 7.4) for three times. Afterwards, 2.0 mM MCH was added and incubated for 30 min to remove nonspecific adsorption sites, followed by washing with Tris–HCl buffer. Whereafter, 10.0 µL of Ag NPs-labeled S2 was added to hybridize with S1 for 10 min (S2/S1/SLAg NPs-PWE) and washed with buffer again (Scheme 2C). At last, the device was stored at 4 °C before further use.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Scheme 2. Illustration of the fabrication procedures and detection process for the 3D ECL-LPD. (A) bare PWE; (B) SLAg NPs/PWE; (C) S2/S1/SLAg NPs-PWE; (D) Pb2+/S2/S1/SLAg NPs-PWE; (E) S3/S1/SLAg NPs-PWE; (F) the current variation of the process.

2.8. The ECL-LPD detection process. The most noteworthy was that the reservoir was filled with Tris–HCl buffer (10 mM, pH 7.4) containing 0.15 mM luminol and 5 mM H2O2 before the detection process. Then, the device was placed in front of the PMT. The scanning range of triggered pressure is from 0~0.8 V and the scan rate is 100 mV·s-1. And then record the ECL intensity and denote it as I1 (in other words I1 was the ECL intensity before the addition of Pb2+). Then, varying concentrations of Pb2+ dissolved in the Tris-acetate buffer (pH 7.4) were pipetted onto the modified working electrode to react for 55 min at room temperature and washed with the buffer (Scheme 2D). Subsequently, the synthesized PFCeO2 NPs modified with S3 (0.5 µM) was added and incubated at room temperature for 105 min (Scheme 2E). After


Page 10 of 30

Page 11 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


hybridization (S3/S1/SLAg NPs-PWE), the electrode was extensively washed with Tris–HCl buffer and dried under a stream of nitrogen prior to electrochemical characterization. The ECL signals related to the Pb2+ concentration could be measured again, which was denoted as I2. And the current variation of the corresponding process was shown in Scheme 2F. 3. RESULTS AND DISCUSSION 3.1. Characterization of SLAg NPs-PWE, Ag NPs and PFCeO2 NPs. The SLAg NPs-PWE was prepared by a simple chemical reduction for in-situ growth of SLAg NPs layer on the PWE to strengthen the conductivity and improve accessible surface area. As shown in the SEM image (Figure 1A), bare paper sample zone with many macropores created a unique attachment microenvironment for growth the SLAg NPs. Figure 1B shows that plenty of SLAg NPs are covered the surface of rough cellulose fibers. As illustrated in Figure 1C, SLAg NPs-PWE exhibits a snowflake shape with a diameter about 6 µm. It is apparent that the beautiful structure substantially increases the specific surface area of the paper-based device. Besides, element mapping was employed to distinguish the distribution of SLAg NPs on the surface of PWE. As shown Figure 1D, three elements, containing Ag, C and O, were distributed on the whole surface of the paper fibers, which clearly confirmed the successful preparation of SLAg NPs-PWE. Moreover, XRD method was used to examine the phase and structure of the SLAg NPs (Figure S2). The diffraction peaks around 22.72, 38.23, 44.46, 64.63 and 77.63 indexed to (002), (111), (200), (220), and (311) planes were observed. Figure S3 shows the EDS image of the prepared SLAg NPs-PWE, which



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

reveals once again that the SLAg NPs-PWE is successfully synthesized.

Figure 1. (A) SEM images of bare PWE; (B and C) the SEM images of SLAg NPs-PWE with different magnifications; (D) the element mapping of the SLAg NPs-PWE.

Figure 2 illustrates the morphology of Ag NPs and PFCeO2 NPs. The Ag NPs were synthesized through a simple chemical reduction. The SEM and TEM images of the Ag NPs are shown in Figure 2A and B. It could be seen that they are crystals with uniform shape and size. And the surfaces of the materials are smooth, and the size of it is about 50 nm. Figure 2C and D show the representative SEM and TEM images of


Page 12 of 30

Page 13 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


PFCeO2 NPs. The PFCeO2 NPs revealed relatively uniform with phoenix tree fruit morphology with an average size of 45 nm. Besides, the TEM image of PFCeO2 NPs exhibits that the material has a well porous nanostructure with a coarse surface, highly branched subunits, and uniform sizes. The EDS analysis (Figure S4) shows that the sample consists of Ce and O elements, indicating the formation of PFCeO2 NPs.

Figure 2. (A) SEM and (B) TEM images of Ag NPs; (C) SEM of PFCeO2 NPs; (D) TEM image of PFCeO2 NPs . Inset in D ( photo of phoenix tree fruit).

3.2. ECL detection of Pb2+. To test the feasibility of the experiment, a series of experiments of signal amplification were tested in lead ion concentration of 1 nM. As shown in the Figure 3A, the ECL signal of SLAg NPs-PWE exhibited a relatively small intensity (curve a). After the Ag NPs-labeled S2 fixed on the electrode surface, the signal had 0.27 times signal decrease (curve b) compared with SLAg NPs-PWE.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 30

When Ag NPs-labeled S2 was replaced by PFCeO2 NPs-labeled S3 (curve c) and the ECL intensity produced 13.6-fold enhancement compared with curve b. To clearly reveal the specific change on the surface of the PWE and the variation of the corresponding luminous intensity of luminol during the step by step modification process, a bar chart was drawn and the result was shown in Figure 3B. 3.3. Characterizations of the stepwise modified electrode. EIS is an effective method to describe the impedance changes in the surface of the PWE during the modification

process.

Its

spectra

were

obtained

in

5.0

mmol·L-1

[Fe(CN)6]4-/[Fe(CN)6]3- solution containing 0.1 mol·L-1 KCl. As illustrated in Figure 3C, bare PWE exhibited a relatively small semicircle with low electron-transfer resistance (Ret) (curve a). When the SLAg NPs layer was modified on the PWE, a lower resistance (curve b) was measured compared with the bare PWE. Then an increased Ret was obtained when S1 was introduced into the surface of the PWE (curve c). With the immobilization of Ag NPs-labeled S2, an apparently increased Ret was discovered (curve d), which was attributed to the fact that Ag NPs conjugated S2 bounded the interfacial electron transfer. After dropped varying concentrations of Pb2+ and PFCeO2 NPs conjugated S3 into the surface of the PWE, the PWE showed a higher resistance due to the poor electroconductibility of PFCeO2 NPs and stereo-hindrance effect of the PFCeO2 NPs-DNA complexes (curve e), which indicates the successful assembly of the biosensor.


Page 15 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 3. (A) and (B): Comparison of ECL responses: (a) SLAg NPs-PWE, (b) S2/S1/SLAg NPs-PWE, and (c) S3/S1/SLAg NPs-PWE in the concentrate of Pb2+ of 1 nM; (C) EIS of (a) bare PWE, (b) SLAg NPs-PWE, (c) S1/SLAg NPs-PWE, (d) S2/S1/SLAg NPs-PWE, (e) S3/S1/SLAg NPs-PWE.

3.4. Optimization of main experimental conditions. In order to obtain high sensitivity for Pb2+ detection, several factors were optimized with 1 nM Pb2+ as a model. Due to luminol served as the luminescent reagents, the effect of luminol concentration on the analytical performance of the 3D paper-based ECL device was investigated. Figure S5 shows the relation between the luminol concentration and the ECL signal. And the relation was divided into two differently stages. The ECL intensity exhibited a rapid rise ranging from 0.05 mM to 0.15 mM. However, the intensity had no clearly change when the concentration of luminol exceeded 0.15 mM. So the optimal concentration of luminol was 0.15 mM. Another factor which has a huge effect on the ECL signal is the pH of buffer. Unsuitable pH can decrease hybridization of the strands and even damage the DNA. It is also a momentous element that recede relationship between the surface of the electrode and the strands. Therefore, a series of experiments in the Tris-HCl with different pH values were



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

tested. In Figure S6, the optimal pH of the buffer solution is about 7.4. Furthermore, the incubation time was crucial for hybridization between S1 and S3 which had a significant influence on the ECL signal. As observed in Figure S7, the ECL intensity extremely increased with the incubation time before 105 min. When the incubation time reached 105 min, there was no obvious increase in ECL intensity. So the incubation time was selected as 105 min. The DNAzyme cleavage time of biosensor is an important parameter which can affect the analytical performance of the 3D ECL-LPD. Only when the S2 would be broken, the intensity returns to the normal level. And then the strands left on the electrode surface can continue hybridize with another strand. Figure S8 shows the dependence of the current intensity along with cleavage time. Considering the optimal analytical performance, 55 min was chosen as optimal cleavage time of biosensor. 3.5. The mechanism of signal amplification. The detection mechanism of the 3D ECL-LPD was described in detail in Scheme 3. SLAg NPs modified PWE was served as a sensing substrate for the analysis of certain amount of Pb2+. Here the modification of SLAg NPs provided a higher electroconductivity and specific surface area. The luminol-H2O2 pair was used as the ECL luminescent reagents. 50 nm Ag NPs, as a quenching agent of luminol-H2O2, were assembled on the surface of SLAg NPs-PWE through the hybridization of the strands (S1+S2), resulting in depressed signal. The reason for this phenomenon is that the absorption peak of Ag NPs (∼425 nm) (Figure 4) is overlap with ECL spectrum of luminol (centered at ∼425 nm), which results in the process happen of the RET from luminol to Ag NPs. Therefore, the ECL emission


Page 16 of 30

Page 17 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


of luminol-H2O2 was greatly quenched.41 To discuss the influence of the size of Ag NPs on the resonance energy transfer from luminol to Ag NPs, the first step is to obtain the Ag NPs with the different sizes. Through altering the reaction time (3 min, 15 min, 45 min, 2 h, 6 h and 8 h), different sizes of the Ag NPs were prepared. As shown in Figure S9, Ag NPs with particle size of 30 nm, 40 nm, 50 nm, 65 nm, 100 nm and 160 nm were obtained. And then, in order to measure the influence, these materials were used to label S2 and the relevant ECL intensities were tested (Figure S10). As shown in the Figure S10, when the reaction time is 45 min, the ECL intensity is the highest one. In other words, the optimal diameter is 50 nm. To explore its reason, UV-vis spectra of samples were measured (Figure S11). As displayed in Figure 4, the absorption peaks of materials are not well overlapped with the emission peak of luminol except for 50 nm. Thus, the emission wavelength of luminol cannot be fully absorbed by Ag NPs with particle size 30 nm, 40 nm, 65 nm, 100 nm, 160 nm. In order to obtain the optimal energy resonance transfer effect, Ag nanoparticles with particle size of 50 nm were selected as signal suppression labels. Meanwhile, in order to prove the SLAg NPs grown on the surface of the PWE has no quenching influence on ECL emission of luminol-H2O2, the absorption peak of SLAg NPs was tested. As shown in Figure 4 curve c, the absorption peak of SLAg NPs is located in ∼290 nm and thus no quenching effect produces on ECL emission of luminol-H2O2.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 4. (a) ECL spectrum of luminol; UV-vis absorption spectra of (b) Ag NPs and (c) SLAg NPs.

After that, the target Pb2+ specifically recognized the sequence of DNAzyme and activated DNAzyme. The activated DNAzyme would catalyze the ribonucleotide (rA) site in S2 to cleave the substrate strand into two DNA fragments.42 In other words, Ag NPs were dropped from the electrode and the ECL signal was recovered without the quenching effect producing by Ag NPs. Subsequently, PFCeO2 NPs-labeled S3 hybridized with S1. And ECL intensity had obvious increase owing to the quick Ce4+ ↔ Ce3+ reaction. The Ce3+ catalyzed H2O2 producing O2•−, which could promote luminescence of luminol, and the ECL signal of luminol was amplified at once.43 The probable mechanism is shown as follows: (LH− is the deprotonated luminol and Ap2-* is 3-aminophthalate) Ce4+ + e− → Ce3+ (1) Ce3+ + H2O2 → Ce4++ O2•− (2) LH− − e− → LH* →L−* + H+ (3) O2•− + L−* → Ap2−* + products (4)


Page 18 of 30

Page 19 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Ap2−* → Ap2−+ hυ (5) Thus, the amount of PFCeO2 NPs increased accordingly upon increasing the concentration of Pb2+, and the ECL intensity is depended on the quantity of PFCeO2 NPs. There is a positive correlation between the increase of the ECL signal and the concentration of Pb2+.

Scheme 3. Detection mechanism of the 3D ECL-LPD

3.6. Analytical performance In order to make better analytical performance, the working curve was plotted under the optimum conditions. As shown in Figure 5A, the change of ECL intensity (I=I2-I1) of the sensor increased accordingly upon increasing the logarithm values of the Pb2+ concentrations, which indicated a good linear relationship in the range from 0.05 to 2000 nM. The linear regression equation is expressed as I=1333.03+929.07lg [Pb2+] ([Pb2+], nM) with the correlation coefficient 0.9967. The detection limit is found to be 0.016 nM based on 3σ calculation. The linear range and detection limit of this work were compared with other approaches (Table S2). According to the table, the limit of detection in this work was much lower



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

than those. In other words, the sensitivity of the device is pretty good. Figure 5B shows the ECL intensity increases with the increasing of time under the different concentrations of Pb2+ in a 10 mM Tris–HCl buffer (pH 7.4) including Pb2+ concentration (nM): (a) 0.05, (b) 0.1, (c) 0.5, (d) 1, (e) 3, (f) 15, (g) 120, (h) 700, (i) 1000, (j) 2000.

Figure 5. (A) Calibration plots of the proposed biosensor; (B) ECL signal of the system to different concentrations of Pb2+ ((a) 0.05, (b) 0.1, (c) 0.5, (d) 1, (e) 3, (f) 15, (g) 120, (h) 700, (i) 1000, (j) 2000 nM) (ten measurements for each point).

3.7 Stability, specificity and reproducibility of the biosensor. The specific recognition of the DNAzyme can influence the accuracy of the samples testing. To examined the specificity of the fabricated biosensor to Pb2+, ten potential interference metal ions (Zn2+, Mg2+, Cu2+, Al3+, Ag+, Fe3+, Hg2+, Na+, K+, Ca2+) with the concentration of 100 nM were measured under the optimum experimental conditions. As expected, a significant ECL signal response to the target Pb2+ was obtained (1 nM), while the ECL signals of the interference ions were extremely small (Figure 6B). The


Page 20 of 30

Page 21 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


results clearly exhibited that the other metal ions do not have the capability to activate the DNAzyme, indicating our developed method with strong anti-interference capacity. Moreover, the reproducibility of the sensor also was a crucial property of the device which was measured by RSD. A series of experiments were determined on five different electrodes with the same Pb2+ concentration. RSD of five dependent measurements was less than 3.7% for the device in same batch (Figure 6A) and 4.3% for the device in different batches. Furthermore, when the device was not in use, it was stored at 4 °C (sealed). The signal of the sensor wasn’t found obvious change after storing for three weeks compared with freshly prepared sensors, which indicated that the reliability of the detection signal was acceptable.

Figure 6. (A) ECL stability of the proposed ECL-LPD to 1 nM Pb2+; (B) Specificity of the detection of Pb2+ (1 nM) against potential interference metal ions (Zn2+, Mg2+, Cu2+, Al3+, Ag+, Fe3+, Hg2+, Na+, K+, Ca2+) with the concentration of 100 nM.

3.8. Application of the sensor in lake water. The practical applicability of the designed sensor was studied by detecting Pb2+ in lake water. Experiments were



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 30

performed by adding various concentrations of Pb2+ into the freshwater samples prepared by simply filtered firstly. Then, several ECL sensors were fabricated by incubation in the diluted lake water samples (pH 7.4). The test was performed using the standard addition method. As results from Table 1, the recovery values were ranging from 97.4 % to 104.0 %, respectively, which indicated that the proposed biosensor was available for determining Pb2+ in real samples.

Table 1 The Determination of Pb2+ in Lake Samples Sample

Add/nM

Found/nM

Recovery/%

lake water

1 80 150 750 1500

1.04 77.92 147.31 748.46 1507.87

104.0±2.0 97.4±3.4 98.2±1.7 99.8±2.6 100.5±1.2

4. CONCLUSION In conclusion, a novel 3D ECL-LPD was developed for sensitive detection of Pb2+ based on SLAg NPs-PWE served as biosensor matrix and PFCeO2 NPs as label for promoting signal amplification. Without the present of Pb2+, the signal was remained in signal off state due to the RET effect between luminol and Ag NPs. However, in the presence of the target, the strands S2 was cleaved by the activated DNAzyme, resulting in the dropping of the Ag NPs and temination of the RET process and further leading to the ECL signal recovery of the device. Importantly, with the introduction of the PFCeO2 NPs which converted H2O2 into O2•− to react with luminol, the signal got a further amplification and turned to signal on state. With the


Page 23 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


dexterous design of the “off-on” switch, the sensitive of our developed detection method was significantly improved. This work demonstrates that a promising detection Pb2+ method, having wide linear range, good stability and excellent selectivity, in the environment monitoring applications is explored through the unique design of enzymatic cleavage from the combination of the high-efficiency RET with the highly sensitive ECL technology.

ASSOCIATED CONTENT Supporting Information The sequences used in this work; The results of comparing with other detection methods; The photos of 3D ECL-LPD for each step; The XRD and EDS image of the SLAg NPs-PWE; The EDS pattern of the PFCeO2 NPs; Optimization of main experimental conditions including luminol concentrations, pH value, incubation time and leavage time; SEM images and UV-vis absorption spectra of Ag NPs obtained under different reaction time and the relevant ECL intensities. AUTHOR CONTRIBUTION Corresponding Author *Tel: +86-531-82767161; Fax: +86-531-82765969; *E-mail address: [email protected]. Author Contributions #

Y.H. and L.L. contributed equallly to this work.

Notes



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The authors declare no competing financial interest. ACKNOWLEDGMENTS This work was financially supported by National Natural Science Foundation of China (51502112, 21475052, 21575051), and Key Research and Development Program of Shandong Province, China (2016GGX102035). REFERENCES (1) Godwin, H. A. The Biological Chemistry of Lead. Curr. Opin. Chem. Biol. 2001, 5, 223-227. (2) Needleman, H. Lead Poisoning. Annu. Rev. Med. 2004, 55, 209-222. (3) Zhao, X. H.; Kong, R. M.; Zhang, X. B.; Meng, H. M.; Liu, W. N.; Tan, W. H.; Shen, G. L.; Yu, R. Q. Graphene-DNAzyme Based Biosensor for Amplified Fluorescence “Turn-On” Detection of Pb2+ with a High Selectivity. Anal. Chem. 2011, 83, 5062-5066. (4) Shi, X.; Gu, W.; Peng, W.; Li, B.; Chen, N.; Zhao, K.; Xian, Y. Sensitive Pb2+ Probe Based on the Fluorescence Quenching by Graphene Oxide and Enhancement of the Leaching of Gold Nanoparticles. ACS Appl. Mater. Interfaces 2014, 6, 2568-2575. (5) Zhu, X.; Gao, X.; Liu, Q.; Lin, Z.; Qiu, B.; Chen, G. Pb2+-Introduced Activation of Horseradish Peroxidase (HRP)-Mimicking DNAzyme. Chem. Commun. 2011, 47, 7437-7439. (6) Kim, H. N.; Ren, W. X.; Kim, J. S.; Yoon, J. Fluorescent and Colorimetric Sensors for Detection of Lead, Cadmium, and Mercury Ions. Chem. Soc. Rev. 2012, 41, 3210-3244. (7) Li, Y.; Wang, L.; Yin, X.; Ding, B.; Sun, G.; Ke, T.; Chen, J.; Yu, J. Colorimetric Strips for Visual Lead Ion Recognition Utilizing Polydiacetylene Embedded Nanofibers. J. Mater. Chem. A 2014, 2, 18304-18312.


Page 24 of 30

Page 25 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(8) Qi, W.; Wu, D.; Zhao, J.; Liu, Z.; Zhang, W.; Zhang, L.; Xu, G. Electrochemiluminescence Resonance Energy Transfer Based on Ru(phen)32+-Doped Silica Nanoparticles and Its Application in “Turn-on” Detection of Ozone. Anal. Chem. 2013, 85, 3207-3212. (9) Hu, L.; Xu, G. Applications and Trends in Electrochemiluminescence. Chem. Soc. Rev. 2010, 39, 3275-3304. (10) Richter, M. M. Electrochemiluminescence (ECL). Chem. Rev. 2004, 104, 3003-3036. (11) Zhang, Y.; Su, M.; Ge, L.; Ge, S.; Yu, J.; Song, X. Synthesis and Characterization of Graphene Nanosheets Attached to Spiky MnO2 Nanospheres and Its Application in Ultrasensitive Immunoassay. Carbon 2013, 57, 22-33. (12) Zhang, Y.; Liu, W.; Ge, S.; Yan, M.; Wang, S.; Yu, J.; Li, N.; Song, X. Multiplexed Sandwich Immunoassays Using Flow-Injection Electrochemiluminescence with Designed Substrate Spatial-Resolved Technique for Detection of Tumor Markers. Biosens. Bioelectron. 2013, 41, 684-690. (13) Gao, W.; Liu, Z.; Qi, L.; Lai, J.; Kitte, S.; Xu. G. Ultrasensitive Glutathione Detection Based on Lucigenin Cathodic Electrochemiluminescence in the Presence of MnO2 Nanosheets. Anal. Chem. 2016, 88, 7654-7659. (14) Duan, R.; Zhou, X.; Xing, D. Electrochemiluminescence Biobarcode Method Based on Cysteamine-Gold Nanoparticle Conjugates. Anal. Chem. 2010, 82, 3099-3103. (15) Ding, S. N.; Xu, J. J.; Chen, H. Y. Enhanced Solid-State Electrochemiluminescence of CdS Nanocrystals Composited with Carbon Nanotubes in H2O2 Solution. Chem. Commun. 2006, 34, 3631-3633. (16) Liu, H.; Xu, S.; He, Z.; Deng, A.; Zhu, J. J. Supersandwich Cytosensor for Selective and



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 26 of 30

Ultrasensitive Detection of Cancer Cells Using Aptamer-DNA Concatamer-Quantum Dots Probes. Anal. Chem. 2013, 85, 3385-3392. (17) Chen, H.; Zhang, H.; Yuan, R.; Chen, S. Novel Double-Potential Electrochemiluminescence Ratiometric Strategy in Enzyme-Based Inhibition Biosensing for Sensitive Detection of Organophosphorus Pesticides. Anal. Chem. 2017, 89, 2823−2829. (18) Nie, Z.; Deiss, F.; Liu, X.; Akbulut, O.; Whitesides, G. M. Integration of Paper-Based Microfluidic Devices with Commercial Electrochemical Readers. Lab Chip 2010, 10, 3163-3169. (19) Zhang, Y.; Li, L.; Zhang, L.; Ge, S.; Yan, M.; Yu, J. In-Situ Synthesized Polypyrrole-Cellulose Conductive Networks for Potentialtunable Foldable Power Paper. Nano Energy 2017, 31, 174-182. (20) Zhang, Y.; Ge, S.; Yu, J. Chemical and Biochemical Analysis on Lab-on-a-Chip Devices Fabricated Using Three-Dimensional Printing. Trends Anal. Chem. 2016, 85, 166-180. (21) Zhang, Y.; Ge, L.; Li, M.; Yan, M.; Ge, S.; Yu, J.; Song, X.; Cao, B. Flexible Paper-Based ZnO

Nanorod

Light-Emittingdiodes

Induced

Multiplexed

Photoelectrochemical

Immunoassay. Chem. Commun. 2014, 50, 1417-1419. (22) Li, L.; Zhang, Y.; Liu, F.; Su, M.; Liang, L.; Ge, S.; Yu, J. Real-Time Visual Determination of the Flux of Hydrogen Sulphide Using a Hollow-Channel Paper Electrode. Chem. Commun. 2015, 51, 14030-14033. (23) Ma, C.; Liu, H.; Tian, T.; Song, X.; Yu J.; Yan, M. A Simple and Rapid Detection Assay for Peptides Based on the Specific Recognition of Aptamer and Signal Amplification of Hybridization Chain Reaction. Biosens. Bioelectron. 2016, 83, 15-18.


Page 27 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(24) Ge, S.; Lan, F.; Liang, L.; Ren, N.; Li, L.; Liu, H.; Yan, M.; Yu, J. Ultrasensitive Photoelectrochemical Biosensing of Cell Surface N-Glycan Expression Based on the Enhancement of NanogoldAssembled Mesoporous Silica Amplified by Graphene Quantum Dots and Hybridization Chain Reaction. ACS Appl. Mater. Interfaces 2017, 9, 6670-6678. (25) Li, L.; Zhang, Y.; Zhang, L. N.; Ge, S. G.; Liu, H. Y.; Ren, N.; Yan, M.; Yu, J. H. Paper-Based Device for Colorimetric and Photoelectrochemical Quantification of the Flux of H2O2 Releasing from MCF-7 Cancer Cells. Anal. Chem. 2016, 88, 5369-5377. (26) Wang, C. C.; Hennek, J. W.; Ainla, A.; Kumar, A. A.; Lan, W. J.; Im, J.; Smith, B. S.; Zhao, M.; Whitesides, G. M. A Paper-Based “Pop-up” Electrochemical Device for Analysis of BetaHydroxybutyrate. Anal. Chem. 2016, 88, 6326-6333. (27) Liu, H.; Xiang, Y.; Lu, Y.; Crooks, R. M. Aptamer-Based Origami Paper Analytical Device for Electrochemical Detection of Adenosine. Angew. Chem. Int. Ed. 2012, 51, 1-5. (28) Nantaphol, S.; Channon, R. B.; Kondo, T.; Siangproh, W.; Chailapakul, O; Henry, C. S. Boron Doped Diamond Paste Electrodes for Microfluidic Paper-Based Analytical Devices. Anal. Chem. 2017, 89, 4100-4107. (29) Li, X.; Liu, X. A Microfluidic Paper-Based Origami Nanobiosensor for Label-Free, Ultrasensitive Immunoassays. Adv. Healthcare Mater. 2016, 5, 1326-1335. (30) Liu, Y.; Xu, Y.; Tian, Y.; Chen, C.; Wang, C. Jiang, X. Functional Nanomaterials Can Optimize the Efficacy of Vaccines. Small 2014, 10, 4505-4520. (31) Zhang, H. Ultrathin Two-Dimensional Nanomaterials. ACS Nano 2015, 9, 9451-9469. (32) Lu, M.; Yang, S.; Ho, Y. P.; Grigsby, C. L.; Leong, K. W.; Huang. T. J. Shape-Controlled Synthesis of Hybrid Nanomaterials via Three-Dimensional Hydrodynamic Focusing. ACS



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Nano 2014, 8, 10026-10034. (33) Abbasi, E.; Milani, M.; Fekri Aval, S.; Kouhi, M.; Akbarzadeh, A.; Tayefi Nasrabadi, H.; Nikasa, P.; Joo, S. W.; Hanifehpour, Y.; Nejati-Koshki, K. Silver Nanoparticles: Synthesis Methods, Bioapplications and Properties. Crit. Rev. Microbiol. 2016, 42, 173-180. (34) Sun, J.; Ma, D; Zhang, H; Liu, X.; Han, X.; Bao, X.; Weinberg, G.; Pfa¨nder, N.; Su D. Toward Monodispersed Silver Nanoparticles with Unusual Thermal Stability. J. Am. Chem. Soc. 2006, 128, 15756-15764. (35) Simo, A.; Polte, J.; Pfander, N.; Vainio, U.; Emmerling, F.; Rademann, K. Formation Mechanism of Silver Nanoparticles Stabilized in Glassy Matrices. J. Am. Chem. Soc. 2012, 134, 18824-18833. (36) Mulvihill, M. J.; Ling, X. Y.; Henzie, J.; Yang, P. Anisotropic Etching of Silver Nanoparticles for Plasmonic Structures Capable of Single-Particle SERS. J. Am. Chem. Soc. 2010, 132, 268-274. (37) Yang, X.; Sun, X.; Lv, Z.; Guo, W.; Du, Y.; Wang E. Ultrasensitive Nucleic Acid Detection Using Confocal Laser Scanning Microscope with High Crystalline Silver Dendrites. Chem. Commun. 2010, 46, 8818-8820. (38) Sun, Y.; Xia, Y. Shape-Controlled Synthesis of Gold and Silver Nanoparticles. Science 2002, 298, 2176-2179. (39) Wei, J.; Yang, Z.; Yang, H.; Sun, T.; Yang, Y. A Mild Solution Strategy for the Synthesis of Mesoporous CeO2 Nanoflowers Derived from Ce(HCOO)3. Cryst. Eng. Comm. 2011, 13, 4950-4955. (40) Ge, L.; Wang, S.; Song, X.; Ge, S.; Yu, J. 3D Origami-Based Multifunction-Integrated


Page 28 of 30

Page 29 of 30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Immunodevice: Low-Cost and Multiplexed Sandwich Chemiluminescence Immunoassay on Microfluidic Paper-Based Analytical Device. Lab Chip 2012, 12, 3150-3158. (41) Shi, H. W.; Zhao, W.; Liu, Z.; Liu, X. C.; Xu, J. J.; Chen. H. Y. Temporal Sensing Platform Based on Bipolar Electrode for the Ultrasensitive Detection of Cancer Cells. Anal. Chem. 2016, 88, 8795-8801. (42) Cui, L.; Wu, J.; Li, J.; Ju, H. Electrochemical Sensor for Lead Cation Sensitized with a DNA Functionalized Porphyrinic Metal-Organic Framework. Anal. Chem. 2015, 87, 10635-10641. (43) Wang, J. X.; Zhuo, Y.; Zhou, Y; Wang, H. J.; Yuan, R.; Chai, Y. Q. Ceria Doped Zinc Oxide Nanoflowers Enhanced Luminol-Based Electrochemiluminescence Immunosensor for Amyloid-β Detection. ACS Appl. Mater. Interfaces 2016, 8, 12968-12975.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Graphic for manuscript


Page 30 of 30

Cerium Dioxide-Mediated Signal âOnâOffâ by Resonance Energy

Recommend Documents

Cerium Dioxide-Mediated Signal âOnâOffâ by Resonance Energy