Simple and Cost-Effective Glucose Detection Based on Carbon

Article pubs.acs.org/ac

Simple and Cost-Effective Glucose Detection Based on Carbon Nanodots Supported on Silver Nanoparticles Jin-Liang Ma,† Bin-Cheng Yin,*,† Xin Wu,§ and Bang-Ce Ye†,‡ †

Downloaded via KAOHSIUNG MEDICAL UNIV on July 25, 2018 at 03:36:14 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

Lab of Biosystem and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai 200237, China ‡ School of Chemistry and Chemical Engineering, Shihezi University, Xinjiang 832000, China § Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai 200433, China S Supporting Information *

ABSTRACT: We present a new glucose oxidase (GOx)mediated strategy for detecting glucose based on carbon nanodots supported on silver nanoparticles (C-dots/AgNPs) as nanocomplexes. The strategy involves three processes: quenching of Cdots’ fluorescence by AgNPs, production of H2O2 from GOxcatalyzed oxidation of glucose, and H2O2-induced etching of AgNPs. In the C-dots/AgNPs complex, AgNPs act as a “nanoquencher” to decrease C-dots fluorescence by surface plasmon-enhanced energy transfer (SPEET) from C-dots (donor) to AgNPs (acceptor). The H2O2 formed by GOxcatalyzed oxidation of glucose etches the AgNPs to silver ions, thus freeing the C-dots from the AgNPs surfaces and restoring the C-dots’ fluorescence. Therefore, the increase in fluorescence depends directly on the concentration of H2O2, which, in turn, depends on the concentration of glucose. The strategy allows the quantitative analysis of glucose with a detection limit of 1.39 μM. The method based on C-dots/AgNPs offers the following advantages: simplicity of design and facile preparation of nanomaterials, as well as low experimental cost, because chemical modification and separation procedures are not needed. and excellent sensitivity. Many fluorescent compounds have been employed for precise analysis of glucose, including organic dyes,8,9 nanoclusters,10,11 and quantum dots.12−14 However, in many cases, the need for modification, lack of suitability to clinical samples, and turn-off mode design cause unavoidable operational complexity, high experimental cost, and unsatisfactory detection limits. Therefore, it is still of great value to explore a simple, modification-free, and cost-effective fluorescent turn-on strategy for glucose detection to cope with complicated biological samples. In a comparison to molecular fluorescence, carbon nanodots (C-dots) have shown distinct advantages due to their superior photostability, tunable emission spectra, low cytotoxicity, and excellent biocompatibility. The emerging utilization of C-dots with unique properties has led to their use in applications ranging from design of sensors to bioimaging.15−18 Many green synthetic approaches for preparation of C-dots have been demonstrated, including laser ablation,19 chemical and thermal oxidation,20,21 microwave synthesis,22,23 and electrochemical oxidation.24,25 Using the synthesized C-dots, silver nanoparticles (AgNPs) can be grown with attached C-dots by heating or irradiating a mixture of Ag(I) ions and C-dots

T

he increasing incidence of diabetes mellitus is becoming a serious public health problem worldwide. The disease is closely related to a glucose metabolic disorder arising from insulin deficiency or resistance.1 As a clinical indicator of diabetes, the effective and accurate determination of blood glucose is essential for monitoring and managing the disease, as well as preventing serious complications such as heart attacks, kidney failure, high blood pressure, nerve damage, and blindness.1 According to the data from the American Diabetes Association (ADA), the amount of glucose in healthy individuals is between 3.9 and 6.1 mM in whole blood or between 3.9 and 6.9 mM in plasma, while in diabetic patients it is more than 6.1 mM in whole blood or 7 mM in plasma. Although blood glucose levels in healthy individuals and diabetic patients are both in the millimolar range, the complicated blood matrix causes serious interferences in glucose detection,2 resulting in the need for sample dilution procedures prior to the analysis. Thus, for point-of-care testing of the resulting low glucose concentrations, a highly sensitive detection method is needed. In recent years, attempts to sense glucose have made use of a multitude of signal outputs, such as chemiluminescence,3 surface-enhanced Raman scattering,4 mass spectrometry,5 colorimetry,6 electrochemistry,7 and fluorescence.8 Among these, fluorescence-based technologies have sparked tremendous interest due to their facile operation, rapid turn-round, © 2016 American Chemical Society

Received: October 31, 2016 Accepted: December 19, 2016 Published: December 19, 2016 1323

DOI: 10.1021/acs.analchem.6b04259 Anal. Chem. 2017, 89, 1323−1328

Article

Analytical Chemistry

further use. For synthesis of C-dots/AgNPs, 1 mM AgNO3 was added into the C-dot solution to give a final concentration of 7.459 μg/mL C-dots, and then 1 mM fresh NaBH4 solution was added, followed by vigorous shaking for 5 min. The solution changed from light-yellow to dark-brown, indicating the formation of C-dots/AgNPs. Glucose Detection. Detection of glucose in buffer was performed with the following two steps. First, a 100 μL sample of glucose with different concentrations was incubated with glucose oxidase (50 μg/mL) in Tris buffer (pH 7.4, 20 mM) at 37 °C for 40 min to yield H2O2 with concentration directly related to the original glucose concentration. Second, 100 μL of C-dots/AgNPs was added to the reaction mixture. After 5 min, the fluorescence spectrum was recorded using excitation at 414 nm. Glucose Detection in Human Serum. The human serum samples of diabetics and healthy controls were obtained from Shanghai Changzheng Hospital. Prior to analysis, the serum samples were centrifuged using an ultrafilter with a 3000 molecular weight cutoff at 7000 rpm for 15 min. The total volume of the reaction system was 200 μL. First, a 100 μL solution containing 2 μL of serum and glucose oxidase (50 μg/ mL) in Tris buffer (pH 7.4, 20 mM) was incubated at 37 °C for 40 min. Second, 100 μL C-dots/AgNPs was added to the reaction mixture. After 5 min, the fluorescence spectrum was recorded using excitation at 414 nm. The written informed consent was obtained from all study participants prior to enrollment, and the study was approved by the ethics committees from the institution involved.

without any additional reducing agents, to produce C-dots supported on silver nanoparticles (C-dots/AgNPs).26−29 Largesized AgNPs (>2 nm) can act as an excellent “nanoquencher” for organic dyes30,31 and QDs,32 which is different from silver nanoclusters (AgNCs) with a few atoms as fluorophore.33,34 It has also been reported that AgNP species prepared using NaBH4 as a reducing agent could be etched by H2O2 as an oxidant.6,35 Herein, to design H2O2-assisted glucose detection, we constructed a C-dots/AgNPs nanocomplex. Silver nitrate and NaBH4 were added to a solution of C-dots prepared by microwave heating of an aqueous mixture of citric acid and urea. The C-dots can be quenched by AgNPs due to their proximity, resulting in surface plasmon-enhanced energy transfer (SPEET) from C-dots (donor) to AgNPs (acceptor). Glucose oxidase (GOx) catalyzes the oxidation of glucose, to produce gluconic acid and H2O2, which etches AgNPs. This results in the release of C-dots and increased fluorescence, allowing quantitative analysis of glucose. This newly developed fluorescence turn-on sensor is not only simple and costeffective but also highly sensitive and selective toward glucose.

■

EXPERIMENTAL SECTION Reagents and Materials. Citric acid and urea were purchased from Lingfeng Chemical Reagent Co. Ltd. (Shanghai, China). Sodium borohydride (NaBH 4) was purchased from Tianlian Fine Chemical Co., Ltd. (Shanghai, China). Glucose oxidase (GOx) was purchased from SigmaAldrich, Inc. (Saint Louis, MO). Fructose, maltose, and mannose were purchased from Solarbio Science and Technology Co. Ltd. (Beijing, China). Silver nitrate (AgNO3), glucose, galactose, sucrose, lactose, and xylose were purchased from Sinopharm Chemical Reagent Co. Ltd. (Shanghai, China). All chemicals used were of analytical reagent, obtained from commercial sources, and directly used without additional purification. The solutions were prepared using distilled water purified by a Milli-Q water purification system (Millipore Corp., Bedford, MA) with an electrical resistance of 18.2 MΩ cm. Instrumentation. UV−vis absorption and fluorescence spectra were recorded with a multidetection microplate reader (Bio-Tek, Winooski, VT) using a transparent 96-well microplate and a black 96-well microplate (Corning Inc., NY), respectively. Transmission electron microscopy (TEM) was obtained using a Jeol JEM-2100 instrument (JEOL Ltd.). Purification of C-dots was performed using a centrifuge 5804 R (Eppendorf) and an ultracentrifuge CP80 MX (HITACHI). Synthetic Procedures for C-Dots and C-Dots/AgNPs. C-dots were fabricated using citric acid and urea according to the previous method with minor revision.22 In a typical experimental procedure, 100 mL of a clear and transparent solution containing 0.3 g citric acid and 0.3 g urea was heated for 4−5 min using a microwave oven (750 W), and the color of the solution changed gradually from colorless to brown. After the reaction mixture cooled to room temperature, a dark-brown solid was obtained, indicating the formation of C-dots. The solid was placed in a vacuum oven at 60 °C and heated for 1 h to remove the residual small molecules. To dissolve the solid adequately, 40 mL of distilled water was added. The aqueous solution of C-dots was purified in a centrifuge (3000 r/min, 20 min) to remove less-fluorescent larger particles. The supernatant solution was ultracentrifuged at 60 000 r/min for 1 h. Then, the obtained precipitate was dissolved into the C-dot stock solution with 0.7459 mg/mL, and stored at 4 °C before

■

RESULTS AND DISCUSSION As depicted in Scheme 1, C-dots/AgNPs nanocomplexes were formed by reducing a mixture of Ag+ and C-dots with NaBH4. Scheme 1. Fluorescence Turn-On Strategy for Glucose Detection Based on Combination of Carbon Nanodots Supported on Silver Nanoparticles and GOx-Mediated Oxidation of Glucose

The Ag ions interact with the surfaces of C-dots via carboxylic acid, amine, and other functional groups on the C-dots. As a result, the fluorescence of C-dots is effectively quenched due to SPEET. However, the structure of C-dots/AgNPs nanocomplex is destroyed by H2O2, leading to the fluorescence recovery of C-dots. GOx can catalyze the oxidation of glucose to gluconic acid by dissolved oxygen, producing H2O2 as a byproduct. When the reaction mixture resulting from GOxcatalyzed oxidation of glucose is added to the C-dots/AgNPs solution, the generated H2O2 etches the AgNPs to silver ions. The fluorescence of C-dots is regained, and the detectable turnon fluorescence signal can be used for the quantitative assay of glucose. 1324

DOI: 10.1021/acs.analchem.6b04259 Anal. Chem. 2017, 89, 1323−1328

Article

Analytical Chemistry

Figure 1. (A) UV−vis absorption spectra of aqueous solution of C-dots, citric acid, and urea. The inset shows photographs of C-dots under UV irradiation. (B) Emission spectra of C-dots at various excitation wavelengths from 340 to 500 nm with an interval of 20 nm. (C) Absorption spectra of C-dots/AgNPs before (green) and after (purple) adding H2O2. Red line represents the excitation spectrum of C-dots at 530 nm emission. In the inset, centrifuge tube 1 (left) shows C-dots while tubes 2 (middle) and 3 (right) are photographs of C-dots/AgNPs after and before adding H2O2, respectively. (D) Emission spectra of C-dots/AgNPs before (green line) and after (blue line) adding H2O2. Red line represents the emission spectrum of free C-dots.

To demonstrate the mechanism of AgNP-assisted fluorescence quenching of C-dots, the optical properties of C-dots and C-dots/AgNPs were investigated. First, the UV absorption spectra of aqueous solutions of C-dots, citric acid, and urea were observed. Figure 1A shows that the C-dots have two peaks, 340 and 410 nm, while citric acid and urea do not exhibit obvious peaks. Also, the inset shows blue fluorescent image of C-dots under UV irradiation, further confirming the synthesis of C-dots. Varying the excitation wavelength from 340 to 500 nm at 20 nm intervals shows that the emission peaks of the Cdot aqueous solution are excitation-wavelength-dependent in the range 450−560 nm (Figure 1B). The strongest fluorescence emission band is located at 530 nm with excitation at 420 nm. Using emission at 530 nm, Figure 1C shows that the highest excitation peak occurs at 414 nm. The absorption bands from the surface functional groups of the C-dots are obtained by Fourier transform infrared spectroscopy (FT-IR). Figure S1 shows that the bands at 3100−3500 cm−1 belong to υ(OH) and υ(NH), which is important to facilitate the hydrophilicity and stability of the C-dots in aqueous state. Absorption bands at 1600−1770 cm−1 are attributed to υ(CO), demonstrating that carboxylic acid may be used as Ag+ binding site. When C-dots were mixed with AgNO3, followed by reduction with NaBH4, C-dots/AgNPs were generated readily. As shown in Figure 1C, the absorption spectrum of C-dots/ AgNPs was blue-shifted compared with that of C-dots. The reaction solution changed from light-yellow to black-brown before and after synthesis of C-dots/AgNPs (tubes marked

with 1 and 3, respectively, in the inset in Figure 1C). The morphologies of C-dots and C-dots/AgNPs were characterized by transmission electron microscopy (TEM). TEM images show that C-dots are well-dispersed with the average diameter of about 2 nm (Figure S2A). When used for the synthesis of Cdots/AgNPs, C-dots can combine efficiently with AgNPs with the diameter of about 10 nm, and only a few are free from AgNPs (Figure S2B). As a result, the fluorescence of C-dots can be quenched with quenching efficiency up to 99.79%. As shown in Figure 1C, there is large overlap between the excitation spectrum of C-dots (centered at 410 nm) and the absorption spectrum of C-dots/AgNPs (at 390 nm), a necessary condition for SPEET. Therefore, the fluorescence quenching of C-dots may be attributed to SPEET from C-dots to AgNPs. As H2O2 is added to the C-dots/AgNPs solution, the absorbance at 390 nm decreases due to etching of the AgNPs. The TEM image of the reaction system after adding H2O2 shows reoccurrence of free C-dots due to etching of AgNPs (Figure S2C). Correspondingly, the fluorescence enhancement was observed in the presence of H2O2 (blue line, Figure 1D). The lack of any change in the fluorescence of C-dots before and after adding H2O2 excludes the possibility that H2O2 directly enhances the fluorescence of C-dots (Figure S3). To improve the sensitivity of the reaction system toward H2O2, we optimized the Ag+ concentration for synthesis of Cdots/AgNPs and the reaction buffer for H2O2-triggered etching of AgNPs. By monitoring the fluorescence ratio (F/F0), where F and F0 are the fluorescence intensities at 530 nm in the 1325

DOI: 10.1021/acs.analchem.6b04259 Anal. Chem. 2017, 89, 1323−1328

Article

Analytical Chemistry

Figure 2. Response of C-dots/AgNPs to H2O2 with different concentration. (A) Fluorescence emission changes with increased H2O2 concentrations (0, 10, 20, 40, 60, 100, 200, 400, 800, 1000 μM). (B) Plot of fluorescence enhancement (F/F0 − 1) vs concentration of H2O2, where F and F0 are the fluorescence intensities at 530 nm in the presence and absence of H2O2, respectively. Inset: plot of linear region from 10 to 100 μM.

Figure 3. Sensitivity investigation on GOx-assisted glucose detection based on C-dots/AgNPs. (A) Fluorescence emission response to glucose at increasing concentrations (0, 2, 4, 10, 20, 40, 80, 100, 200, 400, 800, 1000, 2000, and 4000 μM). (B) Plot of fluorescence enhancement (F/F0−1) vs concentration of glucose, where F and F0 are the fluorescence intensities at 530 nm in the presence and absence of glucose, respectively. Inset: plot of linear region from 2 to 100 μM.

2B shows the calibration curves based on the fluorescence enhancement (F/F0 − 1) versus H2O2 concentration. In the linear region (10, 20, 40, 60, and 100 μM), the regression equation is F/F0 − 1 = 0.2362[H2O2] − 2.2276, with a correlation coefficient R2 of 0.9951. Therefore, glucose detection using the H2O2-dependent signal from GOxcatalyzed glucose is feasible. Since the identity of the buffer affects both H2O2-induced signal production and GOx-mediated enzymatic reaction of glucose, the performance of glucose and GOx was evaluated in four buffers, including HEPES (20 mM HEPES, pH 7.0), PB (phosphate buffer) (3.8 mM NaH2PO4, 6.2 mM Na2HPO4, pH 7.0), MOPS (20 mM MOPS, pH 7.0), and Tris buffer (20 mM Tris, pH 7.4). As shown in Figure S6, the best fluorescence ratio is obtained when the enzymatic reaction occurs in Tris buffer, which is the same as the buffer used in the detection of H2O2. The reaction time of GOx-mediated enzymatic reaction and the amount of GOx are also investigated to obtain optimum performance, because reaction time will affect the amount of produced H2O2, and excess GOx will increase the background signal and the experimental cost. The GOxmediated enzymatic reaction was performed at four time points (0, 20, 40, and 60 min). Figure S7 shows that the fluorescence

presence and absence of H2O2, respectively, we investigated the effect of Ag+ concentration on the fluorescence behavior of the assay system toward H2O2, because the concentration of Ag+ directly affects the synthesis of AgNPs responsible for the background signal, as well as the required amount of H2O2 for recovery of fluorescence of C-dots. As indicated in Figure S4, the final selection of 1 mM Ag+ provides excellent C-dots/ AgNPs to obtain the best fluorescence ratio. On the basis of superior C-dots/AgNPs, we carried out H2O2 detection in three frequently used buffers (MOPS with pH 7.0, phosphate with pH 7.0, and Tris with pH 7.4) at 20 mM concentrations. As shown in Figure S5, the highest fluorescence ratio was obtained in Tris buffer (20 mM, pH 7.4). Therefore, the reaction system was operated in Tris buffer using C-dots/ AgNPs prepared from 1 mM Ag+ as the optimal reaction conditions for H2O2 detection. Using the optimal experimental conditions obtained above, the linear response of the reaction system to H 2 O 2 concentration ranging from 10 to 1000 μM was evaluated. As shown in Figure 2A, the fluorescence of C-dots at 530 nm was gradually enhanced with increasing H2O2 concentration from 0 to 1000 μM, indicating that the correlation between restored fluorescence and H2O2 concentration is dose-dependent. Figure 1326

DOI: 10.1021/acs.analchem.6b04259 Anal. Chem. 2017, 89, 1323−1328

Article

Analytical Chemistry ratio can increase with time and reach the highest value at 40 min. Using 40 min as reaction time, four GOx enzyme concentrations (25, 50, 100, and 200 μg/mL) were chosen to oxidize glucose. The fluorescence enhancement was measured after adding C-dots/AgNPs, and allowing 5 min for AgNP etching. Figure S8 shows that the best fluorescence ratio is obtained using 50 μg/mL GOx. The sensitivity of GOx-mediated glucose detection was evaluated using the above optimum conditions. The fluorescence enhancement was observed for glucose concentrations ranging from 2 to 4000 μM (Figure 3A). As a result of H2O2 produced from the GOx-assisted oxidation of glucose, a gradual increase of fluorescence intensity occurred with increasing glucose concentration, displaying glucose dosedependent fluorescence enhancement. Figure 3B shows a plot of (F/F0 − 1) at 530 nm versus glucose concentration. The inset in Figure 3B shows that the response is linear in the range 2−100 μM glucose. The linear equation is F/F0 − 1 = 0.1019[glucose] − 0.0883 with a correlation coefficient R2 of 0.9992. The detection limit of glucose was calculated to be 1.39 μM (3σb/slope, where σb is the standard deviation of the blank samples). A comparison to previous methods for glucose detection is shown in Table S1. The C-dots/AgNPs-based assay is more sensitive than a number of reported approaches involving nanomaterials (gold nanocluster,11 graphene quantum dots (GODs),36 copper nanoparticles,37 C-dots,38 nanoceria,9 and perylene-modified AgNPs8) except for the methods based on AgNPs-DNA@GQDs and Si-QDs.12,14 However, our proposed method avoids the preparation of thiol-functionalized DNA in AgNPs-DNA@GQDs and the turn-off mode in SiQDs. More importantly, our proposed method is the first example to achieve sensitive detection of glucose using a Cdots/AgNPs nanocomplex. To demonstrate the practical application of our glucose sensor based on C-dots/AgNPs, pretreated human serum samples from diabetics and healthy individuals were analyzed. As an experimental control to evaluate the performance of our method, fresh serum samples (eight diabetics and three healthy individuals) were first analyzed using the commercial Beckman Hexokinase Method at Changzheng Hospital. Subsequently, the same samples were assayed by our proposed method, and the glucose concentrations were calculated using a calibration equation. Table S2 shows the results were comparable to those obtained by the commercial method. These results confirm that our proposed sensing system is applicable to blood glucose analysis with acceptable accuracy. To validate the specificity of the proposed method for detection of glucose compared to similar molecules, we analyzed several different sugars (maltose, sucrose, lactose, galactose, mannose, fructose, and xylose) using the C-dots/ AgNPs method. As shown in Figure 4, the fluorescence enhancements (F/F0 − 1) of analogues are negligible compared to the glucose result. These results demonstrate that the proposed method is highly selective for distinguishing glucose from other sugars.

Figure 4. Selectivity investigation of the proposed method for detection of glucose. The fluorescence enhancement (F/F0 − 1) values in response to 40 μM samples of different targets, where F and F0 are the fluorescence intensities at 530 nm in the presence and absence of the tested target, respectively.

tration. As a consequence, a simple and cost-effective approach with good sensitivity and selectivity based on a C-dots/AgNPs nanocomplex has been developed. Also, the accurate quantitative assay of glucose in human serum samples indicates the potential for the practical application. This work based on C-dots/AgNPs represents a new example of a wide application of C-dots.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.6b04259. FT-IR spectrum, TEM images, the effect of H2O2 on Cdots, details regarding the optimization of reaction conditions, comparison of our method and other nanomaterial-based methods, and clinical sample detection (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Phone/fax: 0086-2164253832. ORCID

Bin-Cheng Yin: 0000-0002-4011-4307 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was jointly supported by the National Natural Science Foundation of China (Grants 21335003, 21675052, 21575089), the Fundamental Research Funds for the Central Universities, the Science Fund for Creative Research Groups (Grant 21421004), and Programme of Introducing Talents of Discipline to Universities (Grant B16017).

■

■

CONCLUSION In summary, we have designed and prepared C-dots/AgNPs using C-dots bound to AgNPs. The fluorescence of C-dots is quenched due to energy transfer between C-dots as donors and AgNPs as acceptors. AgNPs are etched by H2O2 generated from the enzymatic oxidation of glucose by GOx, leading to a fluorescence enhancement response to the glucose concen-

REFERENCES

(1) Nichols, S. P.; Koh, A.; Storm, W. L.; Shin, J. H.; Schoenfisch, M. H. Chem. Rev. 2013, 113, 2528−2549. (2) Zachariou, M.; Hearn, M. T. W. J. Chromatogr. A 2000, 890, 95− 116. (3) Lan, D.; Li, B.; Zhang, Z. Biosens. Bioelectron. 2008, 24, 934−938. 1327

DOI: 10.1021/acs.analchem.6b04259 Anal. Chem. 2017, 89, 1323−1328

Article

Analytical Chemistry (4) Shafer-Peltier, K. E.; Haynes, C. L.; Glucksberg, M. R.; Van Duyne, R. P. J. Am. Chem. Soc. 2003, 125, 588−593. (5) Chen, R.; Xu, W.; Xiong, C.; Zhou, X.; Xiong, S.; Nie, Z.; Mao, L.; Chen, Y.; Chang, H. C. Anal. Chem. 2012, 84, 465−469. (6) Xia, Y.; Ye, J.; Tan, K.; Wang, J.; Yang, G. Anal. Chem. 2013, 85, 6241−6247. (7) Cao, X.; Wang, N.; Jia, S.; Shao, Y. Anal. Chem. 2013, 85, 5040− 5046. (8) Li, J.; Li, Y.; Shahzad, S. A.; Chen, J.; Chen, Y.; Wang, Y.; Yang, M.; Yu, C. Chem. Commun. 2015, 51, 6354−6356. (9) Liu, B.; Sun, Z.; Huang, P. J. J.; Liu, J. J. Am. Chem. Soc. 2015, 137, 1290−1295. (10) Liu, X.; Wang, F.; Niazovelkan, A.; Guo, W.; Willner, I. Nano Lett. 2013, 13, 309−314. (11) Wang, L. L.; Qiao, J.; Liu, H. H.; Hao, J.; Qi, L.; Zhou, X. P.; Li, D.; Nie, Z. X.; Mao, L. Q. Anal. Chem. 2014, 86, 9758−9764. (12) Wang, L.; Zheng, J.; Li, Y.; Yang, S.; Liu, C.; Xiao, Y.; Li, J.; Cao, Z.; Yang, R. Anal. Chem. 2014, 86, 12348−12354. (13) Qu, Z. B.; Zhou, X.; Gu, L.; Lan, R.; Sun, D.; Yu, D.; Shi, G. Chem. Commun. 2013, 49, 9830−9832. (14) Yi, Y.; Deng, J.; Zhang, Y.; Li, H.; Yao, S. Chem. Commun. 2013, 49, 612−614. (15) Ju, E.; Liu, Z.; Du, Y.; Tao, Y.; Ren, J.; Qu, X. ACS Nano 2014, 8, 6014−6023. (16) Liu, C.; Zhang, P.; Tian, F.; Li, W.; Li, F.; Liu, W. J. Mater. Chem. 2011, 21, 13163−13167. (17) Shen, L. M.; Chen, Q.; Sun, Z. Y.; Chen, X. W.; Wang, J. H. Anal. Chem. 2014, 86, 5002−5008. (18) Yuan, C.; Liu, B.; Liu, F.; Han, M. Y.; Zhang, Z. Anal. Chem. 2014, 86, 1123−1130. (19) Xu, X.; Ray, R.; Gu, Y.; Ploehn, H. J.; Gearheart, L.; Raker, K.; Scrivens, W. J. Am. Chem. Soc. 2004, 126, 12736−12737. (20) Bourlinos, A. B.; Stassinopoulos, A.; Anglos, D.; Zboril, R.; Georgakilas, V.; Giannelis, E. P. Chem. Mater. 2008, 20, 4539−4541. (21) Liu, H.; Ye, T.; Mao, C. Angew. Chem., Int. Ed. 2007, 46, 6473− 6475. (22) Qu, S.; Wang, X.; Lu, Q.; Liu, X.; Wang, L. Angew. Chem., Int. Ed. 2012, 51, 12215−12218. (23) Wang, X.; Qu, K.; Xu, B.; Ren, J.; Qu, X. J. Mater. Chem. 2011, 21, 2445−2450. (24) Zhao, Q. L.; Zhang, Z. L.; Huang, B. H.; Peng, J.; Zhang, M.; Pang, D. W. Chem. Commun. 2008, 41, 5116−5118. (25) Zhou, J.; Booker, C.; Li, R.; Zhou, X.; Sham, T. K.; Sun, X.; Ding, Z. J. Am. Chem. Soc. 2007, 129, 744−745. (26) Choi, Y.; Ryu, G. H.; Min, S. H.; Lee, B. R.; Song, M. H.; Lee, Z.; Kim, B. S. ACS Nano 2014, 8, 11377−11385. (27) Shen, L.; Chen, M.; Hu, L.; Chen, X.; Wang, J. Langmuir 2013, 29, 16135−16140. (28) Liu, M.; Chen, W. Nanoscale 2013, 5, 12558−12564. (29) Choi, H.; Ko, S. J.; Choi, Y.; Joo, P.; Kim, T.; Bo, R. L.; Jung, J. W.; Choi, H. J.; Cha, M.; Jeong, J. R.; et al. Nat. Photonics 2013, 7, 732−738. (30) Deng, L.; Ouyang, X.; Jin, J.; Ma, C.; Jiang, Y.; Zheng, J.; Li, J.; Li, Y.; Tan, W.; Yang, R. Anal. Chem. 2013, 85, 8594−8600. (31) Zhou, Z.; Huang, H.; Chen, Y.; Liu, F.; Huang, C. Z.; Li, N. Biosens. Bioelectron. 2014, 52, 367−373. (32) Cao, X.; Shen, F.; Zhang, M.; Sun, C. Sens. Actuators, B 2014, 202, 1175−1182. (33) Ma, J. L.; Yin, B. C.; Le, H. N.; Ye, B. C. ACS Appl. Mater. Interfaces 2015, 7, 12856−12863. (34) Ma, J. L.; Yin, B. C.; Wu, X.; Ye, B. C. Anal. Chem. 2016, 88, 9219−9225. (35) Yang, X.; Yu, Y.; Gao, Z. ACS Nano 2014, 8, 4902−4907. (36) Zhang, L.; Zhang, Z. Y.; Liang, R. P.; Li, Y. H.; Qiu, J. D. Anal. Chem. 2014, 86, 4423−4430. (37) Mao, Z.; Qing, Z.; Qing, T.; Xu, F.; Wen, L.; He, X.; He, D.; Shi, H.; Wang, K. Anal. Chem. 2015, 87, 7454−7460. (38) Shen, P.; Xia, Y. Anal. Chem. 2014, 86, 5323−5329.

1328

DOI: 10.1021/acs.analchem.6b04259 Anal. Chem. 2017, 89, 1323−1328