Chemiluminescence Resonance Energy Transfer Competitive

Subscriber access provided by The University of British Columbia Library

Letter

Chemiluminescence Resonance Energy Transfer Competitive Immunoassay Employing Hapten-Functionalized Quantum Dots for the Detection of Sulfamethazine Mingfang Ma, Kai Wen, Ross C. Beier, Sergei Alexandrovich Eremin, Chenglong Li, Suxia Zhang, Jianzhong Shen, and Zhanhui Wang ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b04171 • Publication Date (Web): 30 Jun 2016 Downloaded from http://pubs.acs.org on July 3, 2016

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 6

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

Chemiluminescence Resonance Energy Transfer Competitive Immunoassay Employing Hapten-Functionalized Quantum Dots for the Detection of Sulfamethazine Mingfang Ma,† Kai Wen,‡ Ross C. Beier,§ Sergei A. Eremin,⊥ Chenglong Li,† Suxia Zhang,†,‡ Jianzhong Shen,†,‡ and Zhanhui Wang*,†,‡ †

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China. ‡ Beijing Laboratory for Food Quality and Safety and Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, No.2 Yuanmingyuan West Road, Beijing 100193, China.

§ Food and Feed Safety Research Unit, Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX 77845, USA. ⊥

Faculty of Chemistry, M. V. Lomonosov Moscow State University, Leninsky Gory, Moscow 119992, Russia.

Supporting Information ABSTRACT: We describe a new strategy for using chemiluminescence resonance energy transfer (CRET) by employing haptenfunctionalized quantum dots (QDs) in a competitive immunoassay for detection of sulfamethazine (SMZ). Core/multishell QDs were synthesized and modified with phospholipid-PEG. The modified QDs were functionalized with the hapten 4-(4-aminophenylsulfonamido)butanoic acid. The CRET-based immunoassay exhibited a limit of detection for SMZ of 9 pg mL–1, which is >4 orders of magnitude better than a homogeneous fluorescence polarization immunoassay and is 2 orders of magnitude better than a heterogeneous enzyme-linked immunosorbent assay. This strategy represents a simple, reliable and universal approach for detection of chemical contaminants. KEYWORDS: quantum dots, chemiluminescence resonance energy transfer, immunoassay, hapten functionalization, chemical contaminant Contamination of food by chemical hazards is a worldwide public health concern and is a leading cause of problems in international trade.1 Consequently, Regulatory Authorities and the food/feed industries have large budgets for monitoring and controlling the safety of food products. These chemical contaminants include a wide range of compounds like veterinary drugs, pesticides, mycotoxins, hormones, packaging components, and drugs of abuse.2 Thus, antibody-based assays, i.e., the immunoassay, is one of the most important techniques for detecting these contaminants in a variety of food samples because of the high sensitivity, specificity, reproducibility, and analysis speed, and are referred to as enzyme-linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFAs) and electrochemical immunoassays.3 However, most immunoassays are heterogeneous and require several separation steps with strict washing procedures, which are timeconsuming and tedious. Therefore, it is necessary to develop a simple and effective homogeneous immunoassay for the detection of chemical contaminants. Unlike the heterogeneous immunoassay that requires binding at a surface, the homogeneous immunoassay binds in solution, drastically reducing the distance that antigens must diffuse to reach the antibodies.4 Combined with the removal of washing steps, the total assay time is reduced, making the homogeneous immunoassay more suitable for rapid detection

applications. Even with these advantages, only a few homogeneous immunoassays for chemical contaminants have been demonstrated including a fluorescence polarization immunoassay (FPIA),5 a fluorescence resonance energy transfer (FRET)6 immunoassay and a luminescence oxygen-channeling immunoassay (LOCI).7 Our group has developed a number of FPIAs during the last decade for chemical contaminants, including antibiotics and mycotoxins, and these studies have shown the advantages of FPIA including decreased assay time, reduced labor and the ability for being fully automated.5,8 However, the overall sensitivity of the FPIA is usually lower compared with the conventional ELISA. The sensitivity may not be acceptable when an analysis needs to be run at trace levels of an analyte. Moreover, limited approaches are available to enhance the FPIA sensitivity in large part because it lacks a signal amplification step during the detection procedure. Another type of homogeneous immunoassay is becoming popular and relies on resonance energy transfer (RET) that occurs between a donor and an acceptor in aqueous solution.9 Several studies have developed the FRET immunoassay for detection of low molecule weight analytes such as explosives, hormones, vitamins and pesticides.10 Compared with the well-established FRET system, the chemiluminescence RET, or CRET, exhibits superior performance that occurs by the oxidation of a luminescent substrate that excites the acceptor without the need for an external light source.11,12 Hence, it can reduce the autofluorescence background and the fluorescence bleaching. Therefore, CRET is an attractive light-measuring scheme useful in bioassays. In the conventional CRET, the fluorophores acting as energy acceptors usually have a small Stokes shift, which result in poor spectral separation between the acceptor emission and the donor emission and low energy-transfer efficiency.11 Semiconductor nanocrystals, known as quantum dots (QDs), have emerged as a unique new class of fluorescence materials over the past decade. QDs are capable of high quantum yield, improved sensitivity and high photostability. They have size-tunable emission wavelengths, and have paved the way for numerous studies including imaging, sensing and targeting biomolecules.3,13 Thus, QDs are now rapidly replacing traditional fluorophores in almost all fluorescence-based applications.14 However, it is only recently that QDs have been applied to CRET systems. Ren et al.15 were the first to demonstrate efficient CRET

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

Page 2 of 6

between luminol as the energy donor and CdTe core QDs as the acceptor, based on an immuno-interaction of BSA-QDs and antiBSA-HRP in the luminol-H2O2 chemiluminescence reaction. Since the work of Ren et al.,15 the QD-based CRET has now been applied to the detection of small molecules (e.g., H2O2, adenosine triphosphate and glucose), DNA and proteins.14,16 In these applications, core or core/shell QDs were used and they were usually functionalized with macromolecules, such as proteins, antibodies, and an aptamer.17 A key approach to improve the detection sensitivity of the CRET-based bioassay is to enhance the CRET efficiency. Although the QD-CRET efficiency is dependent on several factors, the quantum yield of the acceptor QD is the crucial factor to the CRET efficiency;18 that is, a high quantum yield of the QDs results in a high CRET efficiency. Studies have demonstrated that the passivation of core QDs containing multishells strongly increases the luminescence of the QDs up to 35–50% quantum yield.18

Figure 1 (A) HRTEM images (at 2 nm) of QDs and the Inset shows the Fast-Fourier transform of the HRTEM image (dFT(100) =3.50 Å), (B) HRTEM images (at 20 nm) of QDs, (C) HRTEM images (at 50 nm) of QDs, and (D) Hydrodynamic size distribution of the QDs by DLS.

Scheme 1. (A) Schematic illustration of the CRET process between the donor, luminol, and the accepter, QDs, based on the immunoreaction between mAb-HRP and BS-QDs; and (B) Schematic illustration of the CRET-based competitive immunoassay for SMZ.

In spite of the promising possibility offered by CRET, the method has so far only been focused on in vivo imaging studies rather than on the development of bioanalysis. There are no reports of CRET-based immunoassays for small molecule detection, where hapten-functionalized QDs are used to achieve high sensitivity in a competitive immunoassay format. In this study, we developed a CRET-based competitive immunoassay using haptenfunctionalized core/multishell QDs as an energy acceptor for detection of the chemical contaminant, sulfamethazine (SMZ). SMZ was used as a model because it is the most frequently used sulfonamide (SA) in veterinary clinics throughout the world (Figure S1). The performance of the CRET-based immunoassay showed significant superiority compared with the common homogeneous FPIA and heterogeneous ELISA. The assembly of the CRET-based competitive immunoassay for SMZ is shown in Scheme 1. In Scheme 1A, the amphiphilic polymer modified core/multishell QDs were functionalized with the hapten molecule (BS), and the catalyst, HRP, was linked to the specific antibody (mAb4D11) resulting in mAb-HRP. When the mAb-HRP specifically binds to the BS-QDs and the donor luminol was added to the system including H2O2 and enhancer piodophenol, CRET can occur resulting in the increase of fluorescence intensity of BS-QDs. In Scheme 1B, when the analyte SMZ is involved in the CRET system, it can block the CRET process by inhibiting the binding between BS-QDs and mAb-HRP. With an increase in SMZ concentration, it will result in a decrease in fluorescence intensity of the BS-QDs, and the reverse is also true. The highly luminescent core/multishell QDs were prepared in organic solvents according to our previous report (see the Supporting Information (SI)).19 For bioanalytical applications,

a ligand layer is necessary to transfer the hydrophobic QDs to an aqueous solution. Since the original hydrophobic ligands remain on the QD surface, coating the QDs with amphiphilic molecules is preferred to better maintain the initial brightness.20,21 Moreover, the employment of amphiphilic polymers, rather than single molecules or di- or triblock systems, is preferable because polymer chains contain multiple hydrophobic cells which can result in strong interactions with the initial organic coating. Some amphiphilic polymers have been used to modify QDs; however, most of these polymers were home-made through complicated processes and are not commercially available.22–24 In this study, we used a commercially available and low-cost amphiphilic polymer (DSPE-PEG-NH2) to modify the hydrophobic QDs by a reverse-phase evaporation technique (see the SI).19 The size and morphology of the obtained hydrophilic QDs were studied under a high-resolution transmission electron microscope (HRTEM). The HRTEM image of a single modified QD particle revealed high crystallinity with continuous lattice fringes throughout the whole particle (Figure 1A) and the blurry appearance at the rim of this particle may be due to the molecular ligands. The Fourier transform of the HRTEM image (dFT(100) = 3.50 Å) in Figure 1A inset was in good agreement with that of the QD particles prepared by Xie et al.25 Figure 1B and 1C demonstrates the uniform spherical shape of the modified QDs having about a 6.5 nm diameter and being fairly dispersed. In addition to HRTEM analysis, the hydrodynamic diameter of 20.7 nm was also studied by Dynamic Light Scattering (DLS) and shown in Figure 1D. The polydispersity index (PDI) of the QDs size distribution analyzed by DLS was less than 0.1, indicating that the size distribution of the QDs is narrow and also shows good monodispersity. We are the first to describe here hapten functionalized QDs for the development of a CRET-based competitive immunoassay. The carboxylic group of hapten BS was conjugated to the amino group of the QDs using carbodiimide. Prior to the BS-QDs being used in the CRET-based immunoassay, they were characterized with Xray photoelectron spectra (XPS), UV-Vis spectra, fluorescence spectra, HRTEM and immunochemical activity. Figure 2A shows the XPS spectra of the BS-QDs, QDs and BS. High resolution XPS can provide nanoscale sensitivity for analysis of QD surface


Page 3 of 6

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


ligand exchange or conjugation. However, the limitation of XPS in this study rests on the fact that the polymer-modified QDs contain all elements of the hapten BS, resulting in all peaks being integrated. Therefore, qualitative confirmation of the conjugation of BS to the QDs was uncertain, which is similar to the report by Zou et al.26 The highest binding energy peak intensity obtained from the BS-QDs was in agreement with the incorporation of BS molecules to the QDs. Then, the UV-Vis spectrum and the fluorescence spectrum for the QDs and BS-QDs at the same concentration were investigated as shown in Figure 2B. It can be seen that the UV-Vis spectrum (left in Figure 2B) of the QDs was slightly shifted after BS incorporation. The fluorescence spectra (right in Figure 2B) was not shifted but was slightly reduced suggesting it may be due to conjugation of BS to the surface of the QDs resulting in slight fluorescence quenching. This result suggests that the BS molecule does not have much adverse impact on the fluorescence characteristics of the QDs. Subsequently, the immunochemical active BS-QDs were further studied in the CRET-based immunoassay. Two negative control experiments with an anti-ERM mAb-HRP (instead of the anti-SAs mAb-HRP) and the unconjugated QDs without BS and a positive control experiment with addition of conjugated SMZ were performed under identical conditions. Figure 2C shows the fluorescence intensity of the assay obtained under different conditions: BS-QDs+antiSAs mAb-HRP, BS-QDs+anti-SAs mAb-HRP+SMZ, BSQDs+anti-ERM mAb-HRP, and QDs+anti-SAs mAb-HRP. It is not surprising that the highest fluorescence intensity was obtained during the incubation of the BS-QDs and anti-SAs mAb-HRP. A slightly smaller fluorescence intensity was observed in the positive control experiment, which was attributed to the inhibition of the SMZ binding between BS-QDs and the anti-SAs mAb-HRP, resulting in blocking energy transfer. Much less fluorescence intensity was obtained from the two negative control experiments since there was no specific binding occurring between these reagents. These results indicated that the hapten functionalized QDs provided immunochemical activity signifying that the hapten-QDs had a small enough diameter, which guarantee the occurrence of CRET. In addition, the HRTEM in Figure 2D shows the mondispersity of the BS-QDs following functionalization of the QDs with BS. The number of BS molecules per QD was calculated by comparing the concentration of BS and the concentration of QDs in the conjugation solution according to a previous report.26 On average, 16 BS molecules were linked to a single QD. The SDSPAGE study of the QDs and BS-QDs also indicated that the exact mass and charge of the BS-QDs did not significantly increase in the BS functionalized QDs compared to the QDs (see Figure S2). This is in agreement with the characterization by XPS and fluorescence spectra. To develop a highly sensitive CRET-based immunoassay for SMZ, the buffer system and working concentration of the BSQDs was first optimized. As illustrated in Figure 3A, the luminol chemiluminescence intensity at 425 nm in phosphate buffered saline (PBS, 10 mM, pH 7.4) (green line) was higher than the intensity in borate buffer (BB, 50 mM, pH 7.4) (black line) when the BS-QDs were absent in the CRET system under the same conditions. However, the highest fluorescence intensity at 610 nm (inset 3A) was observed when the BS-QDs were added to PBS (blue line) rather than being added to the borate buffer (red line), indicating that in this study, PBS was the more optimal buffer of choice for the chemiluminesence reaction and energy transfer. Unlike sandwich-type immunoassays, the highest sensitivity can be obtained in a competitive immunoassay by having the lowest possible probe (BS-QDs) concentrations theoretically required. Generally, the working concentration of the BS-QDs should be kept close to the minimum detectable concentration for the instrument in use, which will allow a reliable detection of the BS-QDs but does not affect the competition. In this study, the concentra-

Figure 2. (A) XPS measurement of the BS-QDs, QDs and BS, (B) Typical UV-Vis (left, 425 nm) and fluorescence (right, 610 nm) spectra of the QD and BS-QDs, (C) Fluorescent intensity of the assay under different conditions, and (D) HRTEM images (at 20 nm) of the BS-QDs

Figure 3. (A) The chemiluminance intensity and fluorescence intensity (inset) in the CRET-based immunoassay under different conditions, (B) The fluorescence intensity with different concentrations of the BS-QDs, (C) The standard curves for SMZ by CRET, ELISA and FPIA, where S/S0 is the normalized response variable, and (D) Cross-reactivities of the ELISA, FPIA and CRET for SMZ, SMX, SDM and SQX.

tion of BS-QDs was evaluated and the results are shown in Figure 3B, demonstrating that a 1:40 dilution of the original BS-QDs (1 µM) could induce a measurable fluorescence signal and that concentration was selected for use in the assay. Based on the above optimized conditions, a calibration curve (Figure S6) containing various concentrations of SMZ was determined by the immunoassay, and the limit of detection (LOD) was observed at 9 pg mL–1 (3 times the standard deviation of the blank, 3σ) and the analytical range was 0.01–50 ng mL–1. The LOD of the assay was far below the maximum residue limit of SMZ (100 ng mL–1). Since the antiSAs mAb4D11 had broad-specific binding ability,27 three other



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

SA analogs were also used to evaluate the assay specificity. The calibration curves for these SAs are shown in Figure S6B, C, and D, providing cross-reactivities of 100, 539.98, 47.27 and 84.58% for SMZ, sulfadimethoxine (SDM), sulfaquinoxaline (SQX) and sulfamethoxazole (SMX), respectively. To demonstrate the CRET-based immunoassay for SMZ in real samples, we determined the precision (% CV) and the accuracy (% recovery) values of the assay for SMZ at concentrations of 50, 100 and 200 µg L–1 in milk. The accuracy values as expressed in % recovery ranged from 64.7 to 110.7%. The % CV values were less than 10.6% at all concentrations, indicating that the assay may be a potential method for analyzing milk (Table 1). Table 1. Comparisons of analytical performance of CRET with ELISA and FPIAa LOD (ng mL-1)d IC50 (ng mL-1) Detection range (ng mL-1) Assay time (min) Accuracy (% recovery) Precision (% CV)

CRET 0.009 0.2±0.03 0.01–50 < 10 64.7–110.7 < 10.6

ELISAb 0.151 3.084±0.5 0.6–15.7 >180 83.4–102.5 < 16.0

FPIAc 12.1 98.7±4.3 32–145 < 20 75.4–125.3 < 16.3

a

using SMZ as a model analyte b from ref 30, c see supporting information d The data were obtained from the calibration curves in buffer

There are many reports that compare different antibody-based analytical methods for the detection of chemical contaminants such as for microcystins28 and sulfonamides.29 The analytical performance comparison among immunoassays are objective and meaningful only when the same pair of antibody-antigens are employed in the different immunoassay formats. Both the antibody and antigen reagents significantly contribute to the sensitivity and specificity of the immunoassay. In this study, we developed an FPIA for SMZ based on a previously reported ELISA for the detection of SMZ, and we used the same antibody (anti-SAs mAb4D11) and antigen (BS-AMF in the FPIA and BS-BSA in the ELISA).30 The principle, procedure and results of the FPIA for SMZ can be found in the SI section 5, Figure S5, Figure S6 and Table S1. The detailed parameters from the three immunoassays are shown in Table 1 and the standard curves are shown in Figure 3C. The calculated LODs of the FPIA and ELISA for SMZ were 12.1 ng mL–1 and 0.151 ng mL–1 in buffer, respectively (Table 1). The sensitivity of the CRET-based immunoassay for SMZ is more than 4 orders of magnitude better than the FPIA and was even more than 2 orders of magnitude better than the ELISA, indicating that the CRET-based immunoassay incorporating nanomaterials can significantly improve assay sensitivity. The specificities of the three immunoassays were evaluated using three SA analogues other than SMZ and are shown in Figure 3D. The crossreactivities of the immunoassays for the four SAs studied showed similar tendencies, indicating that the recognition profiles of the antibody do not vary as the immunoassay format was changed. We are the first group to describe a homologous CRETbased competitive immunoassay for the detection of SMZ incorporating BS-functionalized core/multishell QDs. This method is an excellent substitute for a FRET-based immunoassay because it eliminates the necessity for an external excitation source. The CRET-based immunoassay exhibited a LOD of 9 pg mL–1, an assay time of 10 min and required no sample preparation. Therefore, the CRET-based immunoassay is a suitable method to be used as a fast, simple, sensitive screening tool for chemical contaminants. By comparison with FPIA and ELISA, the CRET-based immunoassay offers significant advantages. The CRET-based immunoassay developed here can easily be extended to other chemical contaminants by simply changing the targets of interest. Thus,

Page 4 of 6

the CRET-based immunoassay represents a general strategy for food safety residue analysis.

ASSOCIATED CONTENT Supporting Information Experimental details including materials, synthesis and functionalization of multishell QDs, preparation and characterization of mAb-HRP and tracer BS-AMF, development of CRET and FPIA, Figures S1-S7, and Table S1.

AUTHOR INFORMATION Corresponding Author *Email: [email protected]. Fax: 861062731032 Author Contributions All authors have given approval to the final version of the manuscript. Notes The authors declare no competing financial interests.

ACKNOWLEDGMENT The authors would like to thank the National Natural Science Foundation of China (Grant No. 31372475) for financial support.

REFERENCES (1) Şaramet, O.; Gabor, D. O. The Contamination of Food by Chemical Hazards – True Danger for the Fundamental Right to Protection of Health? J. EcoAgriTourism 2010, 6, 147–150. (2) Esteve-Turrillas, F. A.; Abad-Fuentes, A. Applications of Quantum Dots as Probes in Immunosensing of Small-sized Analytes. Biosens. Biolectron. 2013, 41, 12–29. (3) Lei, J.; Ju, H. Signal Amplification Using Functional Nanomaterials for Biosensing. Chem. Soc. Rev. 2012, 41, 2122–2134. (4) Yamanishi, C. D.; Chiu, J. H.-C.; Takayama, S. Systems for Multiplexing Homogeneous Immunoassays. Bioanalysis 2015, 7, 1545–1556. (5) Zhang, H.; Mi, T.; Khan, O. Y.; Sheng, Y.; Eremin, S. A.; Beier, R. C.; Zhang, S.; Shen, J.; Wang, Z. Fluorescence Polarization Immunoassay Using IgY Antibodies for Detection of Valnemulin in Swine Tissue. Anal. Bioanal. Chem. 2015, 407, 7843–7848. (6) Feng, L.; Zhu, A.; Wang, H.; Shi, H. A Nanosensor Based on Quantum-dot Haptens for Rapid, On-site Immunoassay of Cyanotoxin in Environmental Water. Biosens. Bioelectron. 2014, 53, 1–4. (7) Zhang, Y.; Huang, B.; Zhang, J.; Wang, K.; Jin, J. Development of a Homogeneous Immunoassay Based on the AlphaLISA Method for the Detection of Chloramphenicol in Milk, Honey and Eggs. J. Sci. Food Agric. 2012, 92, 1944–1947. (8) Wang, Z.; Liang, X.; Wen, K.; Zhang, S.; Li, C.; Shen, J. A Highly Sensitive and Class-specific Fluorescence Polarisation Assay for Sulphonamides Based on Dihydropteroate Synthase. Biosens. Bioelectron. 2015, 70, 1–4. (9) Algar, W. R.; Kim, H.; Medintz, I. L.; Hildebrandt, N. Emerging Non-traditional Förster Resonance Energy Transfer Configurations with SemiConductor Quantum Dots: Investigations and Applications. Coord. Chem. Rev. 2014, 263–264, 65–85. (10) Medintz, I. L.; Mattoussi, H. Quantum Dot-based Resonance Energy Transfer and Its Growing Application in Biology. Phys. Chem. Chem. Phys. 2009, 11, 17–45. (11) Huang, X.; Ren, J. Nanomaterial-based Chemiluminescence Resonance Energy Transfer: A Strategy to Develop New Analytical Methods. Trend Anal. Chem. 2012, 40, 77–89. (12) Bi, S.; Zhao, T.; Luo, B. A Graphene Oxide Platform for the Assay of Biomolecules Based on Chemiluminescence Resonance Energy Transfer. Chem. Commun. 2012, 48, 106–108. (13) Jiang, S.; Win, K. Y.; Liu, S.; Teng, C. P.; Zheng, Y.; Han, M.-Y. Surface-functionalized Nanoparticles for Biosensing and Imaging-guided Therapeutics. Nanoscale 2013, 5, 3127–3148. (14) Kim, Y.-P. Energy Transfer-based Multiplex Analysis Using Quantum Dots, In Quantum Dots – A Variety of New Applications, AlAhmadi, A. (Ed.), Chapter 11, InTech; 2012, pp 225–240. Available at:


Page 5 of 6

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


http://www.intechopen.com/books/quantum-dots-a-variety-of-newapplications/energy-transfer-based-multiplex-analysis-using-quantumdots. Accessed 16 May 2016. (15) Huang, X.; Li, L.; Qian, H.; Dong, C.; Ren, J. A Resonance Energy Transfer Between Chemiluminescent Donors and Luminescent Quantum-dots as Acceptors (CRET). Angew. Chem. Int. Ed. 2006, 45, 5140– 5143. (16) Qin, G.; Zhao, S.; Huang, Y.; Jiang, J.; Ye, F. Magnetic Beadsensing-platform-based Chemiluminescence Resonance Energy Transfer and Its Immunoassay Application. Anal. Chem. 2012, 84, 2708–2712. (17) Li, Q.; Zhang, L.; Li, J.; Lu, C. Nanomaterial-amplified Chemiluminescence Systems and Their Applications in Bioassays. Trend Anal. Chem. 2011, 30, 401–413. (18) Wang, H.-Q.; Li, Y.-Q.; Wang, J.-H.; Xu, Q.; Li, X.-Q.; Zhao, Y.D. Influence of Quantum Dot's Quantum Yield to Chemiluminescent Resonance Energy Transfer. Anal. Chim. Acta 2008, 610, 68–73. (19) Speranskaya, E. S.; Beloglazova, N. V.; Lenain, P.; De Saeger, S.; Wang, Z.; Zhang, S.; Hens, Z.; Knopp, D.; Niessner, R.; Potapkin, D. V.; Goryacheva, I. Y. Polymer-coated Fluorescent CdSe-based Quantum Dots for Application in Immunoassay. Biosens. Bioelectron. 2014, 53, 225– 231. (20) Karakoti, A. S.; Shukla, R.; Shanker, R.; Singh, S. Surface Functionalization of Quantum Dots for Biological Applications. Adv. Colloid Interface Sci. 2015, 215, 28–45. (21) Blanco-Canosa, J. B.; Wu, M.; Susumu, K.; Petryayeva, E.; Jennings, T. L.; Dawson, P. E.; Algar, W. R.; Medintz, I. L. Recent Progress in the Bioconjugation of Quantum Dots. Coord. Chem. Rev. 2014, 263– 264, 101–137. (22) Fan, H.; Leve, E. W.; Scullin, C.; Gabaldon, J.; Tallant, D.; Bunge, S.; Boyle, T.; Wilson, M. C.; Brinker, C. J. Surfactant-assisted Synthesis of Water-soluble and Biocompatible Semiconductor Quantum Dot Micelles. Nano Lett. 2005, 5, 645–648.

(23) Ren, M.; Xu, H.; Huang, X.; Kuang, M.; Xiong, Y.; Xu, H.; Xu, Y.; Chen, H.; Wang, A. Immunochromatographic Assay for Ultrasensitive Detection of Aflatoxin B1 in Maize by Highly Luminescent Quantum Dot Beads. ACS Appl. Mater. Interfaces 2014, 6, 14215–14222. (24) Li, X.; Li, W.; Yang, Q.; Gong, X.; Guo, W.; Dong, C.; Liu, J.; Xuan, L.; Chang, J. Rapid and Quantitative Detection of Prostate Specific Antigen with a Quantum Dot Nanobeads-based Immunochromatography Test Strip. ACS Appl. Mater. Interfaces 2014, 6, 6406–6414. (25) Xie, R.; Kolb, U.; Li, J.; Basché, T.; Mews, A. Synthesis and Characterization of Highly Luminescent CdSe-core CdS/Zn0.5Cd0.5S/ZnS Multishell Nanocrystals. J. Am. Chem. Soc. 2005, 127, 7480–7488. (26) Zou, Z.; Du, D.; Wang, J.; Smith, J. N.; Timchalk, C.; Li, Y.; Lin, Y. Quantum Dot-based Immunochromatographic Fluorescent Biosensor for Biomonitoring Trichloropyridinol, a Biomarker of Exposure to Chlorpyrifos. Anal. Chem. 2010, 82, 5125–5133. (27) Wang, Z.; Beier, R. C.; Sheng, Y.; Zhang, S.; Jiang, W.; Wang, Z.; Wang, J.; Shen, J. Monoclonal Antibodies with Group Specificity Toward Sulfonamides: Selection of Hapten and Antibody Selectivity. Anal. Bioanal. Chem. 2013, 405, 4027–4037. (28) Tan, F.; Saucedo, N. M.; Ramnani, P.; Mulchandani, A. Label-free Electrical Immunosensor for Highly Sensitive and Specific Detection of Microcystin-LR in Water Samples. Environ. Sci. Technol. 2015, 49, 9256– 9263. (29) Zhou, Q.; Peng, D.; Wang, Y.; Pan, Y.; Wan, D.; Zhang, X.; Yuan, Z. A Novel Hapten and Monoclonal-based Enzyme-linked Immunosorbent Assay for Sulfonamides in Edible Animal Tissues. Food Chem. 2014, 154, 52–62. (30) Liang, X.; Ni, H.; Beier, R. C.; Dong, Y.; Li, J.; Luo, X.; Zhang, S.; Shen, J.; Wang, Z. Highly Broad-specific and Sensitive Enzyme-linked Immunosorbent Assay for Screening Sulfonamides: Assay Optimization and Application to Milk Samples. Food Anal. Methods 2014, 7, 1992– 2002.



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

TOC 53x24mm (600 x 600 DPI)


Page 6 of 6

Chemiluminescence Resonance Energy Transfer Competitive

Recommend Documents