Branch-Migration based Fluorescent Probe for Highly Sensitive

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Letter

Branch-Migration based Fluorescent Probe for Highly Sensitive Detection of Mercury Shanshan Wang, Bin Lin, Li Chen, Na Li, Jiaju Xu, Jing Wang, Yuxiang Yang, Yan Qi, Yongxin She, Xiantao Shen, and Xianjin Xiao Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b03547 • Publication Date (Web): 20 Sep 2018 Downloaded from http://pubs.acs.org on September 20, 2018

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Analytical Chemistry

Branch-Migration based Fluorescent Probe for Highly Sensitive Detection of Mercury Shanshan Wang1,‡, Bin Lin2,3,‡, Li Chen2, Na Li2, Jiaju Xu2, Jing Wang1, Yuxiang Yang2, Yan Qi1, Yongxin She1, Xiantao Shen*,3, and Xianjin Xiao*,2 1

Institute of Quality Standards & Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Key Laboratory of Agrifood Safety and Quality, Ministry of Agriculture of China, Beijing, 100081, P.R. China. 2 Centre of Reproductive Medicine/Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. 3 State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei, 430030, China. ABSTRACT: Detection of heavy metals is of great importance for food safety and environmental analysis. Among various heavy metal ions, mercury ion is one of the most prevalent species. The methods for detection of mercury were numerous and T-Hg-T based assay was promising due to its simplicity and compatibility. However, traditional T-Hg-T based methods mainly relied on multiple T-Hg-T to produce enough conformational changes for further detection, which greatly restrained the limit of detection. Hence, we established a branch-migration based fluorescent probe and found that single T-Hg-T could produce strong signals. The sensing mechanism of our method in different reaction modes was explored and the detection limits were determined to be 18.4 nM and 14.7 nM in first-order reaction mode and mixed reaction mode, respectively. Moreover, coupled with Endonuclease IV assisted signal amplification, the detection limit could be 1.2 nM, lower than most DNA based fluorometric assays. For practicability, the specificity of our assay toward different interfering ions was investigated and detection of Hg2+ in deionized water and lake water was also achieved with similar recoveries compared to those of atomic fluorescence spectrometry, which demonstrated the practicability of our method in real samples. Definitely, the proposed branch migration probe would be a promising substitution for current DNA probes based on recognition of multiple T-Hg-T and we anticipate it to be widely adopted in food and environmental analysis.

Detection of heavy metals is of great importance for food safety and environmental analysis1-4. Among various heavy metal ions, mercury ion is one of the most prevalent species5-7. It could be accumulated by the food chain of the ecological system and thereby was a threat to the food safety of human being8,9. Thus, development of a sensitive and convenient assay for mercury ions is highly demanded. So far, researchers have established various assays for detection of mercury ions, such as atomic absorption spectrometry10,11 and inductively coupled plasma mass spectrometry (ICP-MS)12,13, as well as a series of optical determinaton methods (fluorometric determination methods14-16, colorimetric determination methods17-19, and methods involved surface plasmon resonance (SPR)20,21 or surface-enhanced Raman scattering (SERS)22,23) and electrochemical determination methods24-26. Among these methods, T-Hg-T based assay was promising due to its simplicity and compatibility for biological systems27,28. Furthermore, T-Hg-T based assays were mainly constructed on DNA molecules whose structures were highly flexible for integrating various signal readout pathways or amplification strategies to improve the sensitivity29,30. However, the previously reported T-Hg-T based assays mainly required formation of multiple T-Hg-T to produce enough conformational changes for signal readout3133 . This requirement greatly lowered down the methods’ sensi-

tivity as multiple mercury ions could only cause one DNA probe to produce signals. Therefore, development of a novel type of DNA probe that was sensitive to single T-Hg-T would be greatly preferred. Herein, we have constructed a simple and convenient assay for mercury ions based on branch migration (BM) process and thoroughly characterized the sensing process. The probe was very sensitive to single T-Hg-T and thereby could be an optimal substitution for current DNA probes used in T-Hg-T based assays to improve the sensitivity. Shown in Figure 1a, the proposed probe consisted of three strands: Dabcyl labeled strand (denoted as L-strand and depicted in grey), FAM labeled strand (denoted as S-strand and depicted in blue) and the invading strand (denoted as I-strand and depicted in red). In the design, the S-strand was complementary to the L-strand. So they could form duplexes with single-stranded DNA overhangs. On the other side, the I-strand was also designed to be complementary to the L-strand except for T:T mismatched site. Consequently, the I-strand would hybridize to the ssDNA domain of the L-strand, and the involved three strands would form a branch point within them. Typically, the branch migration process would take place at the branch point34. However, due to its ultra-high sensitivity to slight thermodynamic

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changes, the branch migration process herein was inhibited by the T:T mismatch. At this state, the fluorophore was in close proximity to the quencher, producing very weak background signals. Overall, the involved three strands jointly formed the entire probe for the subsequent detection of mercury ions. As was illustrated in Figure 1a, in the presence of Hg2+, the T:T mismatch would form T-Hg-T, which, in terms of thermodynamics, was as stable as the perfectly matched T:A base pairs. Therefore, the branch migration process could take place, tearing apart the fluorophore and quencher and producing signals.

Figure 1. (a) Schematic illustration of the working principle of our proposed assay. (b) The signals of branch migration probe when treated with or without Hg2+. (c) Effect of the position of T:T mismatch on the increase of fluorescence intensity with a consant length of invading strands.

We firstly verified the working principle of our proposed method. We synthesized S-strand-T, L-strand-T and I-strand-T, and the sequences were shown in Table S1. The L-strand-T and I-strand-T would form a T:T mismatch at the 9th nucleotide 3’ to the I-strand-T (denoted as position +25). The reaction conditions including buffer choice, buffer concentration, buffer pH, ionic strength and temperature were optimized (Figure S1-5 in the supporting information). Under the optimized conditions, we could see that signal of BM probe, which consisted of three strands, remained unchanged throughout the experimental time. In the presence of Hg2+, the fluorescence intensity quickly increased till plateaued (Figure 1b), demonstrating that proposed BM probe was able to sensitively respond to the formation of even single T-Hg-T unit. We then investigated the effect of the location of T:T mismatch on the sensitivity. Using the increase of fluorescence intensity upon same amount of Hg2+, which directly reflected the signal window of the assay, as criterion, we tested all possible locations within the branch migration domain. Experimental results in Figure 1c showed that T:T mismatch located at the middle of the branch migration domain would produce the largest signal window. It was worth noting that the signal plateau in all the tested occasions were nearly the same, so the difference in signal window was mainly attributed to the initial

background fluorescence intensity, which was determined by the inhibition effect of the T:T mismatch on the branch migration process. As was reported in previous literatures, the mismatches located at the middle would cause more destabilization effect than located at the edge35. Therefore, the background fluorescent signal was considerably higher when T:T mismatches located at the beginning and the end of the branch migration domain, which explained the difference in signal window observed in our experiments. As was presented in Figure 1a, the key sensing mechanism of BM probe was based on the sharp drop of the conversion ratio curve over transition free energy around the point where ∆G=0. The detailed thermodynamic model for the conversion ratio curve of the branch migration process was described in the section of materials and methods (See ESI). Therefore, the transition free energy before and after addition of Hg2+, which directly determined the conversion ratio, was vital for the sensitivity of the BM probe toward Hg2+. Actually, with the fixed position of T:T mismatch at the middle of the branch migration domain, we could further change the length of I-strand and thereby change the length of the branch migration domain and the dissociation domain to adjust the transition free energy before and after addition of Hg2+. The initial lengths of docking domain, branch migration domain, and dissociation domain were 18-nt, 7-nt and 24-nt respectively. We then fixed the docking domain at 18-nt, and adjusted the length of the branch migration domain from 7-nt to 26-nt (the corresponding dissociation domain decreased from 24-nt to 5-nt) by gradually increasing the length of I-strand from 25-nt to 44-nt. We used these I-strands to react with same L-strand and Sstrand to compose different BM probes for the detection of Hg2+. Experimental results in Figure 2a showed that when the branch migration domain was shorter than 15-nt (the corresponding dissociation domain was longer than 16-nt), the fluorescent signal toward 1000 nM Hg2+ got its peak with a branch migration domain of 9-nt, which represented the sensitivity of the method. Elongating the branch migration domain from 15nt to 21-nt (shortening the dissociation domain from 16-nt to 10-nt) would gradually enhance the sensitivity. However, further elongating the branch migration domain (shortening the dissociation domain) would greatly lower down the sensitivity. The above phenomenon was also verified by changing the sequence of aforementioned FAM labeled strand and Dabcyl labeled strand. The newly labeled strands were named as S1strand and L1-strand (Table S1). Actually, the sequences of S1-strand and L1-strand were both decreased by 5-nt compared to that of S-strand and L-strand. Besides, the corresponding invading strands were from I2-strand-7 to I2-strand18 (Table S1). So the initial lengths of docking domain, branch migration domain and dissociation domain were 18-nt, 7-nt and 19-nt respectively. Shown in Figure S6, through gradually increasing the length of I-strand, we observed very similar changes of the sensitivity with sharply increased fluoresence intensity when the length of the branch migration domain varied from 12-nt to 15-nt, proximate to the aforementioned result. The above phenomena could be explained from the thermodynamic model and the conversion ratio over transition free energy curve (Figure 2b). When the docking domain and the dissociation domain were both longer than 16-nt, the docking step and dissociation step could be regarded as quasi-complete and quasi-non-reactive respectively. Therefore, the whole


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Analytical Chemistry strand displacement process could be approximated as merely branch migration process (I ⇌ J), namely the first-order reaction mode, corresponding to the Mode III in Figure 2. In this case, the transition free energy before and after addition of Hg2+ remained unchanged regardless of variations of the lengths of the branch migration domain and the dissociation domain, so the sensitivity was almost invariable under such conditions. When the dissociation domain was further shortened, the melting temperature of the dissociation domain would decrease and approach the experiment temperature. Therefore, the dissociation step was no longer quasi-nonreactive, and a fraction of S-strand would dissociate off the Lstrand, which was actually the strand displacement process. As the fluorescent intensity of the fluorophore positively correlated with the distance between the fluorophore and quencher, the dissociation of S-strand could produce considerably stronger signal than hybridized S-strand, which explained the increase of fluorescent signals when elongating I-strand (shortening the dissociation domain). Since a fraction of Sstrand would dissociate off the L-strand, the whole reaction process could not be approximated as I ⇌ J but I + X ⇌ J + Y, corresponding to the mixed mode (Mode II) containing both strand displacement (SD) and branch migration (BM) in Figure 2b. Further elongating I-strand would make the dissociation domain much shorter than the docking domain, and thereby almost all of the S-strand would dissociate off the L-strand and the whole reaction became merely strand displacement (Mode I). In this case, the transition free energy of I + X ⇌ J + Y was significantly below 0, and the corresponding conversion ratio was higher than 50% and even close to 100%. Under such condition, formation of T-Hg-T would produce a same amplitude of negative shift to the transition free energy. But according to the conversion ratio over transition free energy curve, the shift located outside of the sharp-drop domain of the curve, so it would only increase the conversion ratio slightly, which explained the decrease of observed fluorescent signals in Mode I. Conclusively, elongating I-strand would gradually transform the reaction from first-order reaction mode (I ⇌ J) to second-order reaction mode (I + X ⇌ J + Y), and based on above results, BM probe undergoing mixed reaction mode (Mode II in Figure 2) possessed highest sensitivity toward Hg2+. It was worth noting that the mixed reaction mode was relatively variable to different environments. For instance, the slight variation of transition free energy in different environments would cause considerably different distribution of two modes (SD and BM) and thereby instable detection performance. Whereas, due to the very large length of docking domain and dissociation domain, the thermodynamics of firstorder reaction mode (Mode III) was rather stable under different conditions. Comprehensively, we chose the first-order reaction mode and mixed reaction mode for subsequent investigation. We then evaluated the detection limit of our proposed assay using aforementioned two modes, and the detection limit was defined as 3σ/slope, where σ was the relative standard deviation of a blank solution. Before that, we optimized the amount of I-strand and the optimal concentration was 300 nM (Figure S7). We then prepared a series of solutions containing different concentrations of Hg2+ and treated them with BM probes. The invading strand was selected with a branch migration domain of 9-nt in the first-order reaction mode and 21-nt in

the mixed reaction mode, correspongding to the peaks in Figure 2a, respectively. Shown in Figure 3a and Figure 3b, the detection limit in first-order reaction mode and mixed reaction mode were 18.4 nM and 14.7 nM respectively, in accordance

Figure 2. (a) Effect of the length of branch migration domain on the increase of fluorescence intensity using S-strand and L-strand. (b) The conversion ratio over transition free energy curve in different modes. (Mode I: strand displacement; Mode II: the mixed mode containing both strand displacement and branch migration; Mode III: branch migration)

with the aforementioned discussion. Besides, from the insert figures in Figure 3a and Figure 3b, the linear range in firstorder reaction mode was much wider than that in mixed reaction mode, which also demonstrated the discussion that firstorder reaction mode was rather stable under different conditions. We also would like to point out that the essential advantage of our probe was that its recognition of Hg2+ only relied on single T-Hg-T, which was much sensitive than previous DNA probes that required multiple T-Hg-T. We then verified this advantage by evaluating the detection limit when designing one, two and three T:T mismatches into the BM probe. As was demonstrated in Figure 1c, it would produce the largest signal window when the location of T:T mismatch was at the middle of branch migration domain. Hence, the invading strands used here possessed the same length with the T:T mismatch located in the middle of branch migration domain. The invading strands for one, two and three T:T mismatches were I3-strand-



1, I3-strand-2 and I3-strand-3 respectively (Table S1). Shown in Figure 3c, the detection limits were caculated as 37.9 nM, 51.9 nM and 70.4 nM for one, two and three T-Hg-T, respectively, higher than the detection limit when using optimized single T-Hg-T (18.4 nM or 14.7 nM). Also, we could calculate the increase of fluorescence intensity toward 500 nM of Hg2+ when using one, two and three T:T mismatches, and the results were 127619, 69460 and 43750, respectively.The result fully proved that single T:T mismatch could produce much stronger fluorescent signal than multiple T:T mismatches. Moreover, the ratio of aforementioned fluorescence intensity was 2.9:1.6:1, close to the ratio of 3:2:1. We attributed this advantage to two reasons: First, multiple mismatches would make the initial transition free energy far higher than 0 and the corresponding initial conversion ratio very low. According to the conversion ratio curve over transition free energy, the conversion ratio changed very slowly at this range. Therefore, the fluorescent signal, which corresponded to the increase of conversion ratio, was much less. Second, multiple T:T mismatches required multiple Hg2+ to cause one DNA probe to produce signals, directly lowering down the detection limit. Overall, the above data demonstrated that our proposed BM probe was able to sensitively respond to single T-Hg-T and thereby had much lower detection limit than DNA probes responding to multiple T-Hg-T.

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including deionized water excluded Hg2+ by using atomic fluoresence spectrometry (AFS), Hg2+ was deliberately spiked to simulate the contaminated water. Table 1. Recovery rates in different water samples with our method.

Samples

Deionized water Lake water

Added concentration (nM) 50 500 1000 50 500 1000

Detected concentration (nM) 44.98 484.41 1026.02 46.52 452.85 978.11

Relative standard deviation (%) 8.97 1.29 3.62 7.43 1.16 4.15

Recovery rate (%) 90.0 96.9 102.9 93.0 90.6 97.8

The recoveries for addition of 50 nM, 500 nM and 1000 nM of mercury ions were all more than 90% and the relative strand deviations were less than 10% (Table 1). Besides, the results of the determination of mercury in different water samples with our method and AFS technique (Table S3) also illustrated that our proposed method was comparable to the AFS method. Moreover, the stability of the proposed BM probe in different water samples were tested. As shown in Figure S8, the fluorescence intensity of the BM probe was almost invariable in deionized water and lake water within 1 hour, demonstrating that the stability of BM probe in different water sam ples was high enough for not interfering the detection of mercury ions. Overall, the above data firmly demonstrated the practicability of our method in real samples.

Figure 3. (a) The increase of fluorescence intensity over the concentration of Hg2+ in first-order reaction mode. Insert: Calibration curve of the probe with a linear range up to 1000 nM. (b) The increase of fluorescence intensity over the concentration of Hg2+ in mixed reaction mode. Insert: Calibration curve of the probe with a linear range up to 500 nM. (c) The liner results for detection of Hg2+ using one, two and three T:T mismatches. (d) The specificity of our assay toward different interfering ions.

For practicability, we need to inspect the method’s specificity toward different interfering ions. The concentration of Hg2+ was 500 nM, while the concentrations of interfering ions were all 5000 nM. Shown in Figure 3d, we tested 13 interfering ions (Ag+, Cr3+, Fe3+, Cu2+, Pb2+, Al3+, Co2+, Zn2+, La2+, K+, Cd2+, Ca2+, Ni2+), and only Hg2+ could produce significant fluorescent signal, demonstrating the ultra-high specificity of our method. To further evaluate the method’s practicability, we conducted stability experiment and recovery experiment using deionized water and lake water. Since these water samples

Figure 4. (a) Schematic illustration of the working principle of BM probe coupled with Endo IV assisted signal amplification. (b) The increase of fluorescence intensity over the concentration of Hg2+. Insert: Calibration curve of the improved probe with a linear range up to 250 nM.

We would like to point out that the detection limit of our assay was not at the lowest level among all reported assays. Some methods has reached the sub-nanomolar level. However, to achieve such a low detection limit, researchers have to prepare complicated matarials (e.g. triangular silver nanoprism36,


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Analytical Chemistry graphite carbon nitride37) and adopt sensitive signal readout pathways such as electrochemical signals38,39. In comparison, DNA based fluorometric assays are simpler and much more flexible. Actually, compared to most DNA-based fluorometric assays without any signal amplification, our detection limit was among the lowest level. To be more convincing, the present BM probe was coupled with Endo IV assisted signal pathway to enhance the detection performance. As shown in Figure 4, the detection limit could reach 1.2 nM, lower than most reported DNA-based fluorometric assays (Tablse S2). In conclusion, we have established a BM probe based sensitive assay for the detection of mercury ions. Taking advantages of the unique thermodynamics of the branch migration process and carefully adjusting the structures, the BM probe was able to sense the formation of single T-Hg-T and thereby showed higher sensitivity than assays based on the formation of multiple T-Hg-T. Using the simplest signal readout pathway (FRET), the detection limit for Hg2+ could be 14.7 nM, which was considerably lower than the detection limits of probes with two or three T:T mismatches (51.9 nM and 70.4 nM respectively). Moreover, coupled with Endo IV assisted signal amplification, the detection limit could be 1.2 nM, lower than most reported DNA-based fluorometric assays. In addition, specificity, stability and recovery experiments further demonstrated the practicability of our method. Overall, the proposed assay was superior to most DNA-based fluorometric assays for its simplicity, compatibility and high sensitivity. We believe the proposed BM probe would be an ideal substitution for current DNA probes based on recognition of multiple T-Hg-T, and we anticipate it to be widely adopted in food and environmental analysis.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Experimental details including materials and methods, additional figures and tables.

AUTHOR INFORMATION Corresponding Author * E-mail: [email protected] [email protected]

Author Contributions ‡ These authors contributed equally.

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT This work was financially supported by the National Science Foundation of China (No. 21705053 and 81871732), the Natural Science Foundation of Hubei Province (No. 2017CFB117), Hubei Province health and family planning scientific research project (No. J2017Q017), and Wuhan Youth Science and Technology Plan (2017050304010293).

REFERENCES (1) Wang, J.; Shen, H.; Hu, X.; Li, Y.; Li, Z.; Xu, J.; Song, X.; Zeng, H.; Yuan, Q. A targeted “Capture” and “Removal” scavenger

toward multiple pollutants for water remediation based on molecular recognition. Adv. Sci. 2016, 3, 1500289. (2) Battistel, D.; Baldi, F.; Marchetto, D.; Gallo, M.; Daniele, S. A rapid electrochemical procedure for the detection of Hg (0) produced by mercuric-reductase: Application for monitoring Hg-resistant bacteria activity. Environ. Sci. Technol. 2012, 46, 10675-10681. (3) Manna, B.; Raj, C. R. Nanostructured sulfur-doped porous reduced graphene oxide for the ultrasensitive electrochemical detection and efficient removal of Hg (II). ACS Sustainable Chem. Eng. 2018, 6, 6175-6182. (4) Uysal, K.; Emre, Y.; Köse. E. The determination of heavy metal accumulation ratios in muscle, skin and gills of some migratory fish species by inductively coupled plasma-optical emission spectrometry (ICP-OES) in Beymelek Lagoon (Antalya/Turkey). Microchem. J. 2008, 90, 67-70. (5) Guo, Z.; Park, S.; Yoon, J.; Shin, I. Recent progress in the development of near-infrared fluorescent probes for bioimaging applications. Chem. Soc. Rev. 2014, 43, 16-29. (6) Gai, K.; Hoelen, T. P.; Hsu-Kim, H.; Lowry, G. V. Mobility of four common mercury species in model and natural unsaturated soils. Environ. Sci. Technol. 2016, 50, 3342-3351. (7) Ko, S.-K.; Yang, Y.-K.; Tae, J.; Shin, I. In vivo monitoring of mercury ions using a rhodamine-based molecular probe. J. Am. Chem. Soc. 2006, 128, 14150-14155. (8) Sridhara Chary, N.; Kamala, C. T., Samuel Suman Raj, D. Assessing risk of heavy metals from consuming food grown on sewage irrigated soils and food chain transfer. Ecotox. Environ. Safe. 2008, 69, 513-524. (9) Renzoni, A.; Zino, F.; Franchi, E. Mercury levels along the food chain and risk for exposed populations. Environ. Res. 1998, 77, 68-72. (10) Hanna, C. P.; Tyson, J. F.; Mcintosh, S. Determination of total mercury in waters and urine by flow injection atomic absorption spectrometry procedures involving on- and off-line oxidation of organomercury species. Anal. Chem. 1993, 65, 653. (11) Li, Z.; Wei, Q.; Yuan, R.; Zhou, X.; Liu, H.; Shan, H.; Song, Q. A new room temperature ionic liquid 1-butyl-3trimethylsilylimidazolium hexafluorophosphate as a solvent for extraction and preconcentration of mercury with determination by cold vapor atomic absorption spectrometry. Talanta 2007, 71, 68-72. (12) Bushee, D. S. Speciation of mercury using liquid chromatography with detection by inductively coupled plasma mass spectrometry. Analyst 1988, 113, 1167-1170. (13) Fong, B. M. W.; Siu, T. S.; Lee, J. S. K.; Tam, S. Determination of mercury in whole blood and urine by inductively coupled plasma mass spectrometry. J. Anal. Toxicol. 2007, 31, 281-287. (14) Lee, D.-N.; Kim, G.-J.; Kim, H.-J. A fluorescent coumarinylalkyne probe for the selective detection of mercury(II) ion in water. Tetrahedron Lett. 2009, 50, 4766-4768. (15) Liu, Y.; Wang, X.; Wu, H. Reusable DNA-functionalizedgraphene for ultrasensitive mercury (II) detection and removal. Biosens. Bioelectron. 2017, 87, 129-135. (16) Gu, Z.; Zhao, M.; Sheng, Y.; Bentolila, L. A.; Tang, Y. Detection of mercury ion by infrared fluorescent protein and its hydrogelbased paper assay. Anal. Chem. 2011, 83, 2324-2329. (17) Lee, J.-S.; Han, M. S.; Mirkin, C. A. Colorimetric detection of mercuric ion (Hg2+) in aqueous media using DNA-functionalized gold nanoparticles. Angew. Chem. Int. Ed. 2007, 46, 4093-4096. (18) Li, T.; Dong, S.; Wang, E. Label-free colorimetric detection of aqueous mercury ion (Hg2+) using Hg2+-modulated G-quadruplexbased DNAzymes. Anal. Chem. 2009, 81, 2144-2149. (19) Zhang, S.; Zhang, D.; Zhang, X.; Shang, D.; Xue, Z.; Shan, D.; Lu, X. Ultratrace naked-eye colorimetric detection of Hg2+ in wastewater and serum utilizing mercury-stimulated peroxidase mimetic activity of reduced graphene oxide-PEI-Pd nanohybrids. Anal. Chem. 2017, 89, 3538-3544. (20) Jia, S.; Bian, C.; Sun, J.; Tong, J.; Xia, S. A wavelengthmodulated localized surface plasmon resonance (LSPR) optical fiber sensor for sensitive detection of mercury (II) ion by gold nanoparticles-DNA conjugates. Biosens. Bioelectron. 2018, 114, 15-21.



(21) Castillo, J.; Chirinos, J.; Gutiérrez, H.; Cruz, M. L. Surface plasmon resonance sensor based on golden nanoparticles and cold vapour generation technique for the detection of mercury in aqueous samples. Opt. Laser Technol. 2017, 94, 34-39. (22) Sun, Z.; Du, J.; Jing, C. Recent progress in detection of mercury using surface enhanced Raman spectroscopy-A review. J. Environ. Sci. 2016, 39, 134-143. (23) Zheng, P.; Li, M.; Jurevic, R.; Cushing, S. K.; Liu, Y.; Wu, N. A gold nanohole array based surface-enhanced Raman scattering biosensor for detection of silver (I) and mercury (II) in human saliva. Nanoscale 2015, 7, 11005-11012. (24) Zhang, Y.; Zeng, G. M.; Tang, L.; Chen, J.; Zhu, Y.; He, X. X.; He, Y. Electrochemical sensor based on electrodeposited graphene-Au modified electrode and nanoAu carrier amplified signal strategy for attomolar mercury detection. Anal. Chem. 2015, 87, 989996. (25) Ratner, N.; Mandler, D. Electrochemical detection of low concentrations of mercury in water using gold nanoparticles. Anal. Chem. 2015, 87, 5148-5155. (26) Bui, M.-P. N.; Brockgreitens, J.; Ahmed, S.; Abbas, A. Dual detection of nitrate and mercury in water using disposable electrochemical sensors. Biosens. Bioelectron. 2016, 85, 280-286. (27) Long, L.; Tan, X.; Luo, S.; Shi, C. Fluorinated near-infrared fluorescent probes for specific detection of Hg2+ in an aqueous medium and mitochondria of living cells. New J. Chem. 2017, 41, 88998904. (28) Ge, J.; Li, X.-P.; Jiang, J.-H.; Yu, R.-Q. A highly sensitive label-free sensor for mercury ion (Hg2+) by inhibiting thioflavin T as DNA G-quadruplexes fluorescent inducer. Talanta 2014, 122, 85-90. (29) Meng, F.; Xu, H.; Yao, X.; Qin, X.; Jiang, T.; Gao, S.; Zhang, Y.; Yang, D.; Liu, X. Mercury detection based on label-free and isothermal enzyme-free amplified fluorescence platform. Talanta 2017, 162, 368-373. (30) Ma, W.; Sun, M.; Xu, L.; Wang, L.; Kuang, H.; Xu, C. A SERS active gold nanostar dimer for mercury ion detection. Chem. commun. 2013, 49, 4989-4991. (31) Zhou, W.; Ding, J.; Liu, J. 2-aminopurine-modified DNA homopolymers for robust and sensitive detection of mercury and silver. Biosens. Bioelectron. 2017, 87, 171-177. (32) Li, J.; Wang, H.; Guo, Z.; Wang, Y.; Ma, H.; Ren, X.; Du, B.; Wei, Q. A “turn-off” fluorescent biosensor for the detection of mercury (II) based on graphite carbon nitride. Talanta 2016, 162, 46-51. (33) Wang, W.; Kang, T. S.; Chan, P. W.; Lu, J. J.; Chen, X. P.; Leung, C. H.; Ma, D. L. A label-free G-quadruplex-based mercury detection assay employing the exonuclease III-mediated cleavage of T-Hg2+-T mismatched DNA. Sci. Technol. Adv. Mat. 2015, 16, 065004. (34) Xiao, X.; Wu, T.; Xu, L.; Chen, W.; Zhao, M. A branchmigration based fluorescent probe for straightforward, sensitive and specific discrimination of DNA mutations. Nucleic Acids Res. 2017, 45, e90. (35) Igloi, G. L. Variability in the stability of DNA-peptide nucleic acid (PNA) single-base mismatched duplexes: Real-time hybridization during affinity electrophoresis in PNA-containing gels. Proc. Natl. Acad. Sci. USA 1998, 95, 8562-8567. (36) Chen, S.; Tang, J.; Kuang, Y.; Fu, L.; Ma, F.; Yang, Y. Chen, G.; Long, Y. Selective deposition of HgS at the corner sites of triangular silver nanoprism and its tunable LSPR for colorimetric Hg2+ detection. Sens. Actuators B 2015, 221, 1182-1187. (37) Li, J.; Wang, H.; Guo, Z.; Wang, Y.; Ma, H.; Ren, X.; Du, B.; Wei, Q. A “turn-off” fluorescent biosensor for the detection of mercury (II) based on graphite carbon nitride. Talanta 2017, 162, 46-51. (38) Giacomino, A.; Redda, A. R.; Squadrone, S.; Rizzi, M.; Abete, M. C.; Gioia, C. L.; Toniolo, R.; Abollino, O.; Malandrino, M. Anodic stripping voltammetry with gold electrodes as an alternative method for the routine determination of mercury in fish. Comparison with spectroscopic approaches. Food Chem. 2017, 221, 737-745. (39) Kong, R. M.; Zhang, X. B.; Zhang, L. L.; Jin, X. Y.; Huan, S. Y.; Shen, G. L.; Yu, R. Q. An ultrasensitive electrochemical ‘‘turnon’’ label-free biosensor for Hg2+ with AuNP-functionalized reporter DNA as a signal amplifier. Chem. Commun. 2009, 37, 5633-5635.


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