Tunable Fluorescent Silica-Coated Carbon Dots: A Synergistic Effect

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Tunable Fluorescent Silica-Coated Carbon Dots: A Synergistic Effect for Enhancing the Fluorescence Sensing of Extracellular Cu2+ in Rat Brain Yuqing Lin, Chao Wang, Linbo Li, Hao Wang, Kangyu Liu, Keqing Wang, and Bo Li ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.5b08499 • Publication Date (Web): 23 Nov 2015 Downloaded from http://pubs.acs.org on November 24, 2015

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ACS Applied Materials & Interfaces

Tunable Fluorescent Silica-Coated Carbon Dots: A Synergistic Effect for Enhancing the Fluorescence Sensing of Extracellular Cu2+ in Rat Brain

Yuqing Lin,*,† Chao Wang,† Linbo Li,†,‡ Hao Wang,‡ Kangyu Liu,† Keqing Wang,† Bo Li† †

Department of Chemistry, Capital Normal University, Beijing 100048, China

‡

College of Resources Environment and Tourism, Capital Normal University, Beijing

100048, China

Corresponding author at Department of Chemistry, Capital Normal University, Beijing 100048, China Tel.: +86 1068903047; Fax:+86 1068903047 E-mail address: [email protected] (Y. Lin). 1

ACS Paragon Plus Environment


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Abstract: Carbon quantum dots (CDs) combined with self-assembly strategy has paved an innovative way to fabricate novel hybrids to biological analysis. This study demonstrates a new fluorescence platform with enhanced selectivity for copper ions sensing in the striatum of the rat brain following cerebral calm/sepsis process. Here, the fabrication of silica-coated CDs probe is based on the efficient hybridization of APTES which act as a precursor of organosilane self-assembly, with CDs to form silica-coated CDs probe. The fluorescent properties including intensity, fluorescence quantum yield, excitation-independent region, red/blue shift of emission wavelength of probe are tunable through reliable regulating the ratio of CDs and APTES, realizing selectivity and sensitivity-oriented Cu2+ sensing. The as-prepared probe (i.e., 3.33% APTES-0.9 mg mL-1 CDs probe) show a synergistic amplification effect of CDs and APTES on enhancing the fluorescence signal of Cu2+ detection through fluorescent self-quenching. The underlying mechanism can be ascribed to the stronger interaction including chelation and electrostatic attraction between Cu2+ and N and O atoms-containing as well as negatively charged silica-coated CDs than other interference. Interestingly, colorimetric assay and Tyndall effect can be observed and applied to directly distinguish the concentration of Cu2+ by naked eyes. The proposed fluorescent platform here has been successfully applied to monitor the alteration of striatum Cu2+ in rat brain during the cerebral calm/sepsis process. The versatile properties of the probe provide a new and effective fluorescent platform for sensing method in vivo sampled from the rat brain.

KEYWORDS: Carbon quantum dots, APTES, fluorescence, Cu2+ detection, self-quenching

2


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Introduction In the past several decades, nanoparticles (NPs) and self-assembly have motivated a wide research since it paves an innovative way to fabricate novel hybrids adapted by various applications, which is expect to realize both cooperative properties and synergistic effects.1-2 NPs have been developed to diverse categories, such as magnetic,2 metallic,3 silica based,4-5 semiconductor nanocrystals (quantum dots, QDs),6-7 which can be modified and functionalized and have wide applications in biology such as biolabeling, imaging, drug delivery, and optical sensing due to unique size-dependent properties and new comprehensive physical and optical properties.8-11 Silica coating is one of the most popular strategy for nanoparticle surface modification with the assistance of organosilane self-assembly.1-2, 11-14 Mechanistically, organosilanes self-assembly proceeds by the formation of a Si-O-Si bond between the surface and the silanol groups.1 Additionally, wide extension of effective chemical functionalities at the other end of the silane molecules possesses flexible adaptation of the surface for further applications.11 Moreover, this coating technique can allows a cross-linked silica shell into robust hybrid nanocomposites to protect the core nanoparticles

from

the

environment.15

external

In

this

regard,

3-(aminopropyl)triethoxysilane (APTES), a versatile organosilane utilized by silica coating, has been widely adapted by biotechnology purposes on account of its amino terminal group, and water-soluble properties and can form a covalently attached self-assembled monolayer on various substrates.11-12,

16-17

Such a property can be

explored to constitute a sensing strategy for practical application. Although these elaborate reports have been published on silica coating as mentioned above, only a few methods have reported silica-coated nanoparticles 90%, 0.13 µm~9.0 µm, Beijing Scitlion Technology 7



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Co., Ltd), while the sample of CA power was synthesized with KBr wafer technique. Transmission electron microscope (TEM) and high-resolution TEM (HRTEM) images were collected on a JEM-2100F Transmission Electron Microscope (Japan) operated at 200 kV. All pH measurements were performed with a PB-10 digital pH meter (SARTORIUS, Germany). Energy Dispersive X-Ray Spectroscopy (EDX) of 3.33% APTES-0.9 mg mL-1 CDs nanocomposite was characterized by FE-SEM (SU8010, Hitachi, Japan). The solutions containing CDs or APTES or mixture of both were analyzed for ξ-potential values using dynamic light scattering (Zetasizer Nano ZS series, Malvern Instruments) with 633 nm laser wavelength and a measurement angle of 173° (backscatter detection) at 25 ℃.

RESULTS AND DISCUSSION Synthesis and Characterization of 0.9 mg mL-1 CDs, 3.33% APTES, and 3.33% APTES-0.9 mg mL-1 CDs Probe (The Optimized Probe). In this silica coated CDs probe (Scheme 1A), APTES would readily occur with hydrolysis of the alkoxy groups (a step) followed by Si-O-Si condensation reactions to generate silsesquioxanes cross-linked hybrid structures (b step). In such hybrid structure, inorganic network covalently connected to the organic units via van der Waals interaction in the PBS 7.4 solution.1, 37 On the basis of this theory, CDs were entrapped by silica encapsulation, forming silica coated CDs, accompanied with the APTES hydrolysis and condensation reaction processes. Compared with the simple APTES solution, the encapsulation of CDs within a silica shell is mainly driven by the hydrogen bonding interactions between carboxylic ion groups and amino groups (c step), resulting in thermodynamically defined interdigitated “bilayer” structures.1,

26, 38

With the

introduction of Cu2+ into the silica coated CDs solution, the strong interaction including chelation and electrostatic attraction between Cu2+ and N and O atoms-containing as well as negatively charged silica-coated CDs directly lead to the aggregation of silica coated CDs (d step). TEM, HRTEM, FT-IR, FL spectra, and UV-visible absorption spectra have been 8


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demonstrated to characterize and understand the modification process of probes. As shown in Figure 1a, uniform CDs with Φf to be 6.71% (see inset in Figure 1a) have been synthesized through pyrolyzation. The lattice spacing of CDs is around 0.21 nm, which is consistent with that of (100) facet of graphite.39 APTES solution with volume ratio of 3.33% and Φf of 5.43% dry on a copper grid by vacuum drying and then organosilica film layer can observed with a lattice spacing to be around 0.27 nm (Figure 1b). The organosilica film layer is derived from the sol–gel polycondensation of APTES drived by the hydrolysis of the alkoxy groups followed by Si-O-Si condensation reactions to generate silsesquioxanes cross-linked hybrid structures (as illustrated in Scheme 1A, step a) and b).1, 26, 40 Meanwhile, TEM image of optimized probe shows that silica-shelled CDs have an obvious size increment than pristine CDs (Figure 1c), compared with Figure 1d and Figure 1e, size distributions of CDs and optimized are 2.4 ± 1.16 nm and 4.2 ± 2.11 nm, respectively, it is clearly demonstrated that a silica shell (thickness to be approximately 2.5 nm), coated on CDs, can enhance the Φf (15.43) of probe as previous report.11 The elemental analysis result of 3.33% APTES and optimized probe from EDX dates (Table S1, Supporting Information) reveals that the contents of C and O atoms are increased after introducing the CDs due to the feature of carbon and oxygen-riched of CDs.41 Furthermore, the HRTEM of the synthesized optimized probe (Figure 1f) displayed one lattice spacing to be around 0.21 nm being identical with the CDs, suggesting CDs successfully introduced into the probe, while another increased lattice spacing around 0.36 nm emerged in probe larger than APTES, which we speculate that some CDs with smaller size or carboxylic ion groups have imbedded into the lattice spacing of the APTES film and then changed the lattice constant of APTES film during hydrolysis and condensation process of silica encapsulation. The structure of optimized probe shows some similar characterization with CDs and APTES, such as O-H stretching (3233 cm-1), CH2 asymmetric (2935 cm-1), C=O stretching (1642 cm-1) and COO- asymmetric vibration /NH2 scissor vibration (1571 cm-1) and COO- symmetric vibration (1386 cm-1), confirming the APTES successfully hybridized with CDs. The strong peaks at 3496, 3450 and 3294 cm-1 are belong to 9



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O-H stretching, and the double bands at 1754 and 1708 cm-1 are attributed to C=O stretching of the COOH groups (Figure S1, Supporting Information).17, 41

Figure 1. TEM, HRTEM (inset) images and photos illuminated by UV light of 365 nm of (a) 0.9 mg mL-1 CDs, (b) 3.33% APTES, and (c) optimized, Inset: the black dot inside the red circle of (c) represents silica coated CDs, Φf: the fluorescence quantum yield; (d) The size distribution histogram of (a); (e) The size distribution histogram of (c); (f) The HRTEM image of (c).

The FL properties of 0.9 mg mL-1 CDs, 3.33% APTES, and optimized probe are demonstrated in Figure 2. The maximum excitation wavelength of 0.9 mg mL-1 CDs, 3.33% APTES solution, and optimized probe are 338, 349, and 358 nm, respectively, with corresponded maximum emission wavelength at 450, 427, and 446 nm, meanwhile, the blue light emission of optimized probe can be quenched distinctly after adding 4167 µM Cu2+ (the inset of Figure 2A). Here, the FL properties of APTES solution is ascribe to the quantum confinement process and the quantum confinement-luminescence center process from the nanoscale-Si-particle (Figure S2, Supporting Information).42 Under the excitation of 365 nm, the emission spectra of 10


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them show that the maximum emission wavelength of optimized probe is between 0.9 mg mL-1 CDs and 3.33% APTES (Figure S3, Supporting Information). The UV−vis absorption spectra shows only one absorption band of APTES centered at 299 nm, the same well-defined absorption trait at 363 nm is reflected in both 0.9 mg mL-1 CDs and optimized probe. Remarkably, emission spectra of them (Figure S4, Supporting Information) at different excitation wavelength (λEX) indicates that 3.33% APTES solution

is

excitation-dependent

and

0.9

mg

mL-1

CDs

is

partial

excitation-independent with λEX from 260 to 300 nm. After 3.33% APTES solution incorporated with 0.9 mg mL-1 CDs, the hybrid (i.e., optimized probe) also show a large partial excitation-independent region from 260 to 340 nm. The origin of such behavior can be ascribed to that both the size and the surface state of those sp2 clusters belonged to CDs should be more uniform than APTES.41 Interestingly, the optimized probe shows a more broad and excitation-independent emission, which implied that the APTES film coated on CDs can further make the size and the surface state of those sp2 clusters in CDs more uniform. Based on the results obtained as aforementioned, the developed optimized probe possesses synergistic effects based on cooperating with the properties of APTES and CDs, respectively.

(B)

(A)

Volume fractions of APTES

Blue Shift

(C)

Concentration of CDs

Red Shift

Figure 2. (A) UV absorption spectra (a, b, c) and FL spectra (excitation spectra: d, e, f; emission spectra: g, h, i) of optimized solution (red curves), 3.33% APTES solution (blue curves), and 0.9 mg mL-1 CDs solution (black curves). Inset: photographs of solution of optimized before (left) and after (right) addition of 4167 µM Cu2+ under 11



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UV light of 365 nm. (B) Dependent FL response of APTES-CDs solutions with fixed concentration of 0.267 mg mL-1 CDs and different volume fractions of APTES. (C) Dependent FL response of APTES-CDs solutions with fixed volume fractions of 3.33% APTES and different concentration of CDs.

Design and Optimization of Cu2+ sensing by CDs, APTES, and APTES-CDs Probes. CDs are one of the most attractive nano carbon materials due to its excellent FL properties. As shown in Figure S5 (Supporting Information), CDs solutions demonstrate a concentration-dependent FL response property and are almost not interfered by 10 µM Cu2+ excited at 365 nm, i.e., the FL intensity of CDs is increased with concentration decreasing from 44.5 to 1 mg mL-1, while it decreased with concentrations below 1 mg mL-1, which can be ascribed to high CCDs suffer from FL self-quenching induced by closely adjacent CDs and low CCDs lack of enough available fluorophores.27 As to a biosensing assay process in analytical chemistry, sample dilution is always involved and any background interferences involved in detection process induced by dilution must be avoid.43 Therefore, the CCDs from 1 to 44.5 mg mL-1 is not suitable for subsequent experiments since dilution strategy involved in this concentrations range, leading to an increased intensity of background interference. In view of this point, 0.267 mg mL-1 CDs solutions (green dot in Figure S5) are firstly used to investigate the hybridization with different volume fraction of APTES. As displayed in Figure 2B, a series of VAPTES from 0 to 3.33% have been incorporated with fixed concentration of 0.267 mg mL-1 of CDs solutions, forming different APTES-0.267 mg mL-1 CDs sensing systems. The FL spectra show a blue shift with the increasing of the VAPTES, which can be ascribed to the polarization effect.44 Subsequently, anti-interference ability of APTES-0.267 mg mL-1 CDs to specific metal ions (10 µM), such as Cu2+, Fe3+, Hg2+, Ag+, Ni2+, Mg2+, K+, Na+, Ca2+, Zn2+, Co2+, Cd2+, and Pb2+ are investigated. After mixed with Cu2+, VAPTES in the probes from 0.33% to 1.33% show an FL enhancement effect accompanied by stronger interference by other cations. Whereas, a FL quenching effect is observed 12


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with the VAPTES from 2% to 3.33% (Figure S6, Supporting Information), which indicated high VAPTES is benefit for Cu2+ sensing and thus different CCDs with fixed volume fractions of 3.33% APTES based probes (3.33% APTES-CDs) were further investigated (Figure 2C). Compared with the FL spectra of Figure 2B, the FL spectra obviously shift to red direction with the increasing of CCDs from 0 to 0.9 mg mL-1, attributing to the polarization effect and hydrogen bonding in the solution (Figure 2C).44-46 According to the Vivian’ research, the blue shift and the red shift of FL spectra in this work can be also attributed to the electric field imposed by the CDs and APTES, they may be termed an internal Stark effect.47 Furthermore, the interference results of specific metal ions to Cu2+ exhibit that 3.33% APTES-CDs probes illustrate a prominent enhanced sensitivity and selectivity to Cu2+ based on fluorescent quenching effect with the increasing of CCDs (Figure S6F, Figure S7, Supporting Information and Figure 3). Meanwhile, as demonstrated in Figure S8 (Supporting Information), it was found that FL response of 0.9 mg mL-1 CDs and 3.33% APTES solutions are almost not affected by different cations, however, Cu2+ has a more strong FL response to both 0.9 mg mL-1 CDs and 3.33% APTES solutions than other cations, no matter fluorescent enhancement effect on 3.33% APTES or quenching effect on 0.9 mg mL-1 CDs. Importantly, after the integration of 3.33% APTES and 0.9 mg mL-1 CDs, the sensing signal of optimized probe is stronger than any other APTES-CDs based probes already described (Figure S6, S7, Supporting Information and Figure 3) and the pure APTES and the CDs. These results can be explained by the higher thermodynamic affinity and faster chelating process of Cu2+ with N and O atoms of APTES and CDs than other cations, which pave the way of high selectivity of as-synthesized optimized probe.7,

25, 27-30

For better sensing performances, the pH

values were also studied, as shown in Figure S9, the sensing property of the optimized probe under low basic conditions is better than weak acid conditions. Considering the hydrolysis of Cu2+ and physiological nature of the sample, pH 7.4 has employed for real sample analysis. 13



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(A)

(B)

Figure 3. (A) FL response of the optimized to different physiological species in pH 7.4 PBS solution. Metal ions selectivity: 10 µM for Cu2+, Fe3+, Hg2+, Ag+, Ni2+, Zn2+, Co2+, Cd2+, Pb2+ and 1 mM for K+, Na+, Ca2+, and Mg2+. Biomolecules selectivity: 10 µM for UA, DOPAC, AA, DA; 5 µM for Cys, Gly, L-Glu (Glutamic); 1 µM for H2O2, and 1 mM for Glu (Glucose). (B) Competition experiments with the subsequent addition of 10 µM Cu2+ to the 3.33% APTES-0.9 mg mL-1 CDs solution containing biological species same as (A). F0 and F1 are the emission fluorescence intensities excited at 365 nm of 3.33% APTES-0.9 mg mL-1 CDs solutions in the absence and presence of biological species, respectively.

Mechanism of Cu2+ Detection by Silica Coated CDs. Generally, mechanism involved in fluorescent sensing based on quantum dots (QDs) quenching effect include Förster resonance energy transfer (FRET),9 inner filter effect (IFE),48 redox reaction occurs on the QDs surface,49 and electron/energy transfer.7 In this study, firstly, fluorophores can be quenched through dynamic quenching effect (DQE) or 14


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static quenching effect (SQE) or both simultaneously.50-51 The dependence of fluorescence quenching on copper ion are analyzed by the Stern–Volmer equation (F0/F1=KSV [Q] + 1, where F0 and F1 are the PL intensity of QDs in the absence and presence of the quencher (i.e., copper ions), respectively, [Q] is the concentration of the quencher, and Ksv is the Stern-Volmer constant.). The plot falls in non-linearity relationship, indicating DQE and SQE are both involved in the fluorescence quenching process. Moreover fluorescence lifetime measurement are investigated in Figure 4B to verify as mentioned, in which fluorescence decay time of optimized probe, optimized probe + 0.833 µM Cu2+, and optimized probe + 416.7µM Cu2+ are different with each other at a large deviation, i.e., 9.38, 10.3 and 8.28 µs, respectively.

(A)

(B)

Figure 4. (A) Stern–Volmer plot for Cu2+ concentration dependence of fluorescence intensity of optimized probes. (B) Fluorescence decay profile of optimized probe (red dot), optimized probe + 0.833 µM Cu2+ (black dot), and optimized probe + 416.7µM Cu2+ (green dot).

To understand the Cu2+ sensing character appears with respect to the selectivity to other metal ions, VAPTES and CCDs value can modulate the electrostatic interaction between the silica coated CDs (Figure S10, Supporting Information). As for APTES-0.267 mg mL-1 CDs based probes, low VAPTES (0.33% to 1.33%) can lead to the electrostatic repulsion decrease. However, with the increasing of VAPTES from 2% 15



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to 3.33%, the outermost of silica coated CDs may be decorated with more amino groups, resulting in the electrostatic repulsion increased with ξ-potential values increasing from -2.71 to -3.96 mV, thus, the FL quenching here caused by Cu2+ can be considered as that the electrostatic attraction originated from the strong chelation of Cu2+ with N and O atoms from silica-shelled CDs is greater than corresponding electrostatic repulsion, which directly induce the adjacent silica coated CDs into close contacting and even aggregation and then fluorescent self-quenching (Scheme 1 and Figure S11, Supporting Information). Furthermore, since Cu2+ is a paramagnetic ion with an unfilled d shell, electron/energy transfer might be a profound factor making fluorescence quenching of Cu2+ more obviously than other mental ions.7,31 On the other hand, the ξ-potential values of 3.33% APTES-CDs based probes increased with the increase of CCDs, which indicates that increasing of CCD can improve the stability of APTES-CDs system. Therefore, 3.33% APTES-CDs probe with concentration of 0.9 mg mL-1 CDs is selected as optimized probe for practical applications. (A)

R2=0.990

(B)

16


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Figure 5. (A) FL responses of optimized probes in PBS (pH 7.4) with Cu2+ (from up to bottom) of 0, 0.833, 4.167, 8.33, 41.67, 83.3, 166.7, 416.7, 833, 1667, 2500, 4167 µM. Inset: (Upper) photographs from 1 to 12 are corresponded to the samples with different concentration of Cu2+ from FL measurements while the photograph 13 is optimized probe with 6250 µM Cu2+. The image inside the red dashed box refers to the partial enlarged detail of photograph 13. (Right lower) Plot of F1/F0 against logarithm (log) of the Cu2+ concentration. F0 and F1 are the emission fluorescence intensities excited at 365 nm of optimized probe solution in the absence and presence of Cu2+, respectively. (B) The images of Tyndall effect show the deionized water, optimized probe, optimized probe + 0.01 µM Cu2+ (1), optimized probe + 4167 µM Cu2+ (2), and optimized probe + 6250 µM Cu2+ (3) in bright field (upper section) and illuminated by a red laser in dark field (lower section). Analytical Performances of Optimized Probe for Cu2+ Detection. Under the optimized conditions discussed above, the analytical performances of optimized probe were further investigated. As described in Figure 5A, the intensity of optimized probe decreased linearly with the concentration of Cu2+ in the wide range from 0.833 to 833 µM [F1/F0 = 0.998 - 0.111*log([Cu2+]), R2= 0.990], the detection limit was calculated to be ~0.3 µM (based on a signal-to-noise ratio of S/N = 3). It is worth mentioned that the content of copper element in deionized water was measured to ~0.012 µM by ICP-MS, which is far below the detection limit, implying the accuracy of the synthesized probe without background interference. Besides, with the increasing of concentration of Cu2+, the color of samples (vials 1 to 13, upper in Figure 5A) with different concentration of Cu2+ change from colorless to deep yellow, accompanied by the precipitation of silica coated CDs due to the aggregation under concentration of Cu2+ higher than 2.5 mM (red dashed box in Figure 5A), i.e., the developed probe can distinguish the concentration of Cu2+ with colorimetric assay by naked eyes. Furthermore, Tyndall effect observing by laser in the Figure 5B fundamentally verified that the probe is a sol system and the light path of probes can be broaden with the increasing of concentration of Cu2+, notably, the scattering spots within the light 17



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path of probes is attributed to tiny aggregations of silica-shelled CDs, which endows the synthesized probe a versatile platform for further applications.

(A)

(B)

Surgical after

Figure 6. (A) FL response of optimized probes in PBS (pH 7.4) with addition of different normal rat brain microdialysates from rat 1, rat 2, and rat 3. (B) Time-dependent concentration of striatum Cu2+ sensing by the present method and ICP-MS method during the cerebral calm/sepsis process with cecal ligation and puncture surgical. Error bars represent the standard deviations of different rats with n= 3.The brain microdialysate was collected every 1h in the surgeries of the cerebral calm/ sepsis process. Fluorescent Sensing of Physiological Cu2+ by Optimized Probe During the Cerebral Calm/sepsis Process. To evaluate the performance the as-prepared fluorescent probes in this study, fluorescent sensing of physiological Cu2+ in biological fluids is a preferred strategy.17, 52 Here, striatum Cu2+ levels in the rat brain microdialysates were investigated during the cerebral calm/sepsis process. As shown in the Figure 6, the FL response of three normal rat (native group) brain microdialysates is distinguishable, by calculating the FL intensities obtained with the linear relationship from Figure 5, the basal level of Cu2+ in three rat brain microdialysates estimated to be 1.81 ± 0.25 µM (mean ± SD), which agree with the reported values.17, 52 To confirm the accuracy of the fluorescent probe during sensing 18


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process, the traditional and standard ICP-MS method for detecting atoms was used as a control method. As exhibited in Table 1, the mean concentration of Cu2+ of same batch samples of three rats is 1.85 ± 0.31 with the RSD of 2.21 ± 0.24%, confirming the determination results of the present method are acceptable, which provides the feasibility of further practical Cu2+ sensing. Therefore, we first applied the proposed fluorescent platform to monitor the alteration of concentration of Cu2+ during the process of sepsis. As described in Figure 7, Cu2+ sensing by the present method reveals that the concentration of striatum Cu2+ has a slightly increase from 1.69 ± 0.23 µM (calm condition) to 2.19 ± 0.18 µM in 1 hour after cecal ligation and puncture surgical and follow by decreasing, however, 5 hour later, the concentration of striatum Cu2+ increased dramatically again to 5.45 ± 0.36 µM and then decreased to calm condition of 1.7 ± 0.28 µM in 8 hour later, which is consistent with the results observed by ICP-MS method. Meanwhile, all animals displayed signs of encephalopathy at 6 to 8 h after sepsis (lethargy, mild ataxia, lack of spontaneous movement), which is similar to previous report.35, 53 Table 1. Detected Results of Physiological Cu2+ levels in Normal Rat Brain Microdialysates by the Present Method and by ICP-MS.

Cu2+ (µM)

Cu2+ levels in rat brain microdialysates mean ± SD rat 1 rat 2 rat 3 (n=3)

present Method

2.06

1.77

1.61

1.81 ± 0.25

ICP-MS

2.18

1.70

1.66

1.85 ± 0.31

CONCLUSION A novel and facile silica-coated carbon dots (CDs) based fluorescence platform with enhanced selectivity for monitoring of cerebral Cu2+ has been developed. Here, The fluorescence platform shows a synergistic amplification effect of CDs and APTES on enhenceing the FL signal of Cu2+ detection through fluorescent self-quenching induced by the stronger interaction, including chelation and electrostatic attraction, between Cu2+ and N and O atoms of negatively charged silica-coated CDs than other 19



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interference. Additionally, colorimetric assay by naked eyes and Tyndall effect can also distinguish the concentration of Cu2+ with the proposed fluorescence platform. Furthermore, the versatile fluorescence platform has been used to monitor the alteration of striatum Cu2+ in rat brain during the cerebral calm/sepsis process with improved selectivity and sensitivity. This study not only pave a new way to sensing of Cu2+ but also provides a new insight into the further application of silica coated semiconductor NPs.

ASSOCIATED CONTENT Supporting Information Available Additional information as noted in the text. This material is available free of charge via the Internet at http://pubs.acs.org. ACKNOWLEDGMENTS This research is financially supported by National Natural Science Foundation (21375088), Scientific Research Project of Beijing Educational Committee (KM201410028006), Youth Talent Project of the Beijing Municipal Commission of Education (CIT&TCD201504072), Scientific Research Base Development Program of the Beijing Municipal Commission of Education and the 2013 Program of Scientific Research Foundation for the Returned Overseas Chinese Scholars of Beijing Municipality.

REFERENCES 1. Chemtob, A.; Ni, L.; Croutxe-Barghorn, C.; Boury, B. Ordered Hybrids from Template-Free Organosilane Self-Assembly. Chem. Eur. J. 2014, 20, 1790-1806. 20


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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


2. Yi, D. K.; Selvan, S. T.; Lee, S. S.; Papaefthymiou, G. C.; Kundaliya, D. J.; Ying, Y. Silica-Coated Nanocomposites of Magnetic Nanoparticles and Quantum Dots. J. Am. Chem. Soc. 2005, 127, 4990-4991. 3. Gong, K.; Su, D.; Adzic, R. R. Platinum-monolayer Shell on AuNi0.5Fe Nanoparticle Core Electrocatalyst with High Activity and Stability for the Oxygen Reduction Reaction. J. Am. Chem. Soc. 2010, 132, 14364-14366. 4. Zhang, H. D.; Dunphy, R.; Jiang, X.; Meng, H.; Sun, B.; Tarn, D.; Xue, M.; Wang, X.; Lin, S.; Ji, Z.; Li, R.; Garcia, F. L.; Yang, J.; Kirk, M. L.; Xia, T.; Zink, J. I.; Nel, A.; Brinker, C. J. Processing Pathway Dependence of Amorphous Silica Nanoparticle Toxicity: Colloidal vs Pyrolytic. J. Am. Chem. Soc. 2012, 134, 15790-15804; 5. Das, S.; Debnath, N.; Cui, Y.; Unrine, J.; Palli, S. R. Chitosan, Carbon Quantum Dot, and Silica Nanoparticle Mediated dsRNA Delivery for Gene Silencing in Aedes aegypti: A Comparative Analysis. ACS Appl. Mater. Interfaces 2015, 7, 19530-19535. 6. Ha, H. D.; Han, D. J.; Choi, J. S.; Park, M.; Seo. T. S. Dual role of Blue Luminescent MoS2 Quantum Dots in Fluorescence Resonance Energy Transfer Phenomenon. Small 2014, 10, 3858-3862. 7. Liu, S.; Tian, J.; Wang, L.; Zhang, Y.; Qin, X.; Luo, Y.; Asiri, A. M.; Al-Youbi, A. O.; Sun, X. Hydrothermal Treatment of Grass: A Low Cost, Green Route to Nitrogen-doped, Carbon-rich, Photoluminescent Polymer Nanodots that can be used as an Effective Fluorescent Sensing Platform for Label-free Sensitive and Selective Detection of Cu(II) Ions. Adv. Mater. 2012, 24, 2037-2041。 8. Makki, R.; Ji, X.; Mattoussi, H.; Steinbock, O. Self-Organized Tubular Structures 21



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

as Platforms for Quantum Dots. J. Am. Chem. Soc. 2014, 136, 6463-6469. 9. Li, L.; Wang, C.; Liu, K.; Wang, Y.; Liu, K.; Lin, Y. Hexagonal Cobalt Oxyhydroxide-Carbon Dots Hybridized Surface: High Sensitive Fluorescence Turn-on Probe for Monitoring of Ascorbic Acid in Rat Brain Following Brain Ischemia. Anal. Chem. 2015, 87, 3404-3411. 10. Merino, S.; Martín, C.; Kostarelos, K.; Prato, M.; Vázquez, E. Nanocomposite Hydrogels: 3D Polymer–Nanoparticle Synergies for On-Demand Drug Delivery. ACS Nano 2015, 9, 4686-4697. 11. Zheng, M.; Xie, Z.; Qu, D.; Li, D.; Du, P.; Jing, X.; Sun, Z. On–Off–On Fluorescent Carbon Dot Nanosensor for Recognition of Chromium(VI) and Ascorbic Acid Based on the Inner Filter Effect. ACS Appl. Mater. Interfaces 2013, 5, 13242-13247. 12. Selvan, S. T., Patra, P. K.; Ang, C. Y.; Ying, J. Y. Synthesis of Silica-Coated Semiconductor and Magnetic Quantum Dots and Their Use in the Imaging of Live Cells. Angew. Chem., Int. Ed. 2007, 46, 2448-2452. 13. Ulman, A. Formation and Structure of Self-Assembled Monolayers. Chem. Rev. 1996, 96, 1533-1554. 14. Zhao, S.; Jiang, B.; Maeder, T.; Muralt, P.; Kim, N.; Matam, S. K.; Jeong, E.; Han, Y-L.; Koebel. M. M. Single Quantum Dot-Micelles Coated with Silica Shell as Potentially Non-Cytotoxic Fluorescent Cell Tracers. ACS Appl. Mater. Interfaces 2015, 7, 18803-18814. 15. Smith, S. R.; Leitch, J. J.; Zhou, C.; Mirza, J.; Li, S.-B.; Tian, X.-D.; Huang, 22


Page 22 of 29

Page 23 of 29

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


Y.-F.; Tian, Z.-Q.; Baron, J. Y.; Choi, Y.; Lipkowski, J. Quantitative SHINERS Analysis of Temporal Changes in the Passive Layer at a Gold Electrode Surface in a Thiosulfate Solution. Anal. Chem. 2015, 87, 3791-3799. 16.

Pasternack,

R.

M.;

Amy,

S.

R.;

Chabal,

Y.

J.

Attachment

of

3-(Aminopropyl)triethoxysilane on Silicon Oxide Surfaces: Dependence on Solution Temperature. Langmuir 2008, 24, 12963-12971. 17. Shao, X.; Gu, H.; Wang, Z.; Chai, X.; Tian, Y.; Shi, G. Highly Selective Electrochemical Strategy for Monitoring of Cerebral Cu2+ Based on a Carbon Dot-TPEA Hybridized Surface. Anal. Chem. 2013, 85, 418-425. 18. Gaggelli, E.; Kozlowski, H.; Valensin, D.; Valensin, G. Copper Homeostasis and Neurodegenerative Disorders (Alzheimer's, Prion, and Parkinson's Diseases and Amyotrophic Lateral Sclerosis). Chem. Rev. 2006, 106, 1995-2044. 19. Pramanik, D.; Ghosh, C.; Dey, S. G. Heme–Cu Bound Aβ Peptides: Spectroscopic Characterization, Reactivity, and Relevance to Alzheimer’s Disease. J. Am. Chem. Soc. 2011, 133, 15545-15552. 20. Zhu, A.; Ding, C.; Tian, Y. A Two-photon Ratiometric Fluorescence Probe for Cupric Ions in Live Cells and Tissues. Sci. Rep. 2013, 3, 2933:1-6. 21. Li, L.; Li, L.; Wang, C.; Liu, K.; Zhu, R.; Qiang, H.; Lin, Y. Synthesis of Nitrogen-doped and Amino Acid-functionalized Graphene Quantum Dots from Glycine, and Their Application to the Fluorometric Determination of Ferric Ion. Microchim. Acta 2014, 182, 763-770. 22. Baker, S. N. ; Baker ,G. A. Luminescent Carbon Nanodots: Emergent Nanolights. 23



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

Angew. Chem., Int. Ed. 2010, 49, 6726-6744. 23. Wang, Y.; Hu, A. Carbon Quantum Dots: Synthesis, Properties and Applications. J. Mater. Chem. C 2014, 2, 6921-6939. 24. Qu, Q.; Zhu, A.; Shao, X.; Shi, G.; Tian, Y. Development of a Carbon Quantum Dots-based Fluorescent Cu2+ Probe Suitable for Living Cell Imaging. Chem. Commun. 2012, 48, 5473-5475. 25. Zhu, A.; Qu, Q.; Shao, X.; Kong, B.; Tian, Y. Carbon-Dot-Based Dual-Emission Nanohybrid Produces a Ratiometric Fluorescent Sensor for In Vivo Imaging of Cellular Copper Ions. Angew. Chem., Int. Ed. 2012, 51,7185-7189. 26. Fan, H. Y.; Chen, Z.; Brinker, C. J.; Clawson, J.; Alam, T. Synthesis of Organo-Silane Functionalized Nanocrystal Micelles and Their Self-Assembly. J. Am. Chem. Soc. 2005, 127, 13746-13747. 27. Generalov, R.; Kavaliauskiene, S.; Westrom, S.; Kristensen, W. S.; Juzenas, P. Entrapment in Phospholipid Vesicles Quenches Photoactivity of Quantum Dots. Int. J. Nanomed. 2011, 6, 1875-1888. 28. Zong, C.; Ai, K.; Zhang, G.; Li, H.; Lu, L. Dual-Emission Fluorescent Silica Nanoparticle-Based Probe for Ultrasensitive Detection of Cu2+. Anal. Chem. 2011, 83, 3126-3132. 29. Chan,Y.-H.; Jin, Y.; Wu, C.; Chiu, D. T. Copper(II) and Iron(II) Ion Sensing with Semiconducting Polymer Dots. Chem. Commun. 2011, 47, 2820-2822. 30. Li, Z.; Zhang, L.; Wang, L.; Guo, Y.; Cai, L.; Yu, M.; Wei. L. Highly Sensitive and Selective Fluorescent Sensor for Zn2+/Cu2+ and New Approach for Sensing Cu2+ 24


Page 24 of 29

Page 25 of 29

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


by Central Metal Displacement. Chem. Commun. 2011, 47, 5798-5800. 31. Rahimi, Y.; Goulding, A.; Shrestha, S.; Mirpuri, S.; Deo, S. K. Mechanism of Copper Induced Fluorescence Quenching of Red Fluorescent Protein, DsRed. Biochem. Biophys. Res. Commun. 2008, 370, 57-61. 32. Lin, Y.; Liu, K.; Yu, P.; Xiang, L.; Li, X.; Mao, L. A Facile Electrochemical Method for Simultaneous and On-Line Measurements of Glucose and Lactate in Brain Microdialysate with Prussian Blue as the Electrocatalyst for Reduction of Hydrogen Peroxide. Anal. Chem. 2007, 79, 9577-9583. 33. Lin, Y.; Zhu, N.; Yu, P.; Su, L.; Mao, L. Physiologically Relevant Online Electrochemical Method for Continuous and Simultaneous Monitoring of Striatum Glucose and Lactate Following Global Cerebral Ischemia/Reperfusion. Anal. Chem. 2009, 81, 2067-2074. 34. Lin, Y.; Yu, P.; Hao, J.; Wang, Y.; Ohsaka, T.; Mao, L. Continuous and Simultaneous Electrochemical Measurements of Glucose, Lactate, and Ascorbate in Rat Brain Following Brain Ischemia. Anal. Chem. 2014, 86, 3895-3901. 35. Erbas, O.; Taskiran, D. Sepsis-induced Changes in Behavioral Stereo typy in Rats; Involvement of TNF-α, Oxidative Stress and Dopamine Turnover. J. Surg. Res. 2014, 186. 262-268. 36. Rittirsch, D.; Huber-Lang, M. S.; Flierl, M. A.; Ward, P. A. Immunodesign of Experimental Sepsis by Cecal Ligation and Puncture. Nat. Protoc. 2008, 4, 31-36. 37. Lehn, J.-M. Toward Self-Organization and Complex Matter. Science 2002, 295, 2400-2403. 25



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

38. Pellegrino, T.; Manna, L.; Kudera, S.; Liedl, T.; Koktysh, D.; Rogach, A. L.; Keller, S.; Rädler, J.; Natile, G.; Parak,W. J. Hydrophobic Nanocrystals Coated with an Amphiphilic Polymer Shell: A General Route to Water Soluble Nanocrystals. Nano Lett. 2004, 4. 703-707. 39. Dong, Y.; Wang, R.; Li, H.; Shao, J.; Chi, Y.; Lin, X.; Chen, G. Polyamine-Functionalized Carbon Quantum Dots for Chemical Sensing. Carbon 2012, 50, 2810-2815. 40. Bluemel, J. Reactions of Ethoxysilanes with Silica: A Solid-State NMR Study. J. Am. Chem. Soc. 1995, 117, 2112-2113. 41. Dong, Y.; Shao, J.; Chen, C.; Li, H.; Wang, R.; Chi, Y.; Lin, X.; Chen, J. Blue Luminescent Graphene Quantum Dots and Graphene Oxide Prepared by Tuning the Carbonization Degree of Citric Acid. Carbon 2012, 50, 4738-4743. 42. Qin ,G. G.; Li,Y. Photoluminescence Mechanism Model for Oxidized Porous Silicon and Nanoscale-silicon-particle-embedded Silicon Oxide. J. Phys. Rev. B. 2003, 68, 085309. 43. Xia, Y.; Ye,Y. J.; Tan, K.; Wang, J.;Yang, G. Colorimetric Visualization of Glucose at the Submicromole Level in Serum by a Homogenous Silver Nanoprism–Glucose Oxidase System. Anal. Chem. 2013, 85, 6241-6247. 44. Bulović, V.; Shoustikov, A.; Baldo, M. A.; Bose, E.; Kozlov, V. G.; Thompson, M. E.; Forrest, S. R. Bright, Saturated, Red-to-Yellow Organic Light-Eemitting Devices Based on Polarization-induced Spectral Shifts. Chem. Phys. Lett. 1998, 287, 455-460. 26


Page 26 of 29

Page 27 of 29

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


45. Kalinowski, J.; Stampor, W. P.; Marco, Di.; Fattori, V. Electroabsorption Study of Excited

States

in

Hydrogen-Bonding

Solids:

Epindolidone

and

Linear

Transquinacridone. Chem. Phys. 1994, 182, 341-352. 46. Alabugin, I. V.; Manoharan, M.; Peabody, S.; Weinhold, F. Electronic Basis of Improper Hydrogen Bonding: A Subtle Balance of Hyperconjugation and Rehybridization. J. Am. Chem. Soc. 2003, 125, 5973-5987. 47. Vivian, J. T.; Callis, P. R. Mechanisms of Tryptophan Fluorescence Shifts in Proteins. Biophys. J. 2001, 80, 2093-2109. 48. Dong,Y.; Wang, R.; Li, G.; Chen, C.; Chi, Y.; Chen, G. Polyamine-Functionalized Carbon Quantum Dots as Fluorescent Probes for Selective and Sensitive Detection of Copper Ions. Anal. Chem. 2012, 84, 6220-6224. 49. Lu, L.; Yang, G.; Xia, Y. From Pair to Single: Sole Fluorophore for Ratiometric Sensing by Dual-Emitting Quantum Dots. Anal. Chem. 2014, 86, 6188-6191. 50. Chan, Y. -H.; Chen, J.; Liu, Q.; Wark, S. E.; Son, D. H.; Batteas, J. D. Ultrasensitive Copper(II) Detection Using Plasmon-Enhanced and Photo-Brightened Luminescence of CdSe Quantum Dots. Anal. Chem. 2010, 82, 3671-3678. 51. Zhai, W.; Wang, C.; Yu, P.; Wang, Y.; Mao, L. Single-Layer MnO2 Nanosheets Suppressed Fluorescence of 7-Hydroxycoumarin: Mechanistic Study and Application for Sensitive Sensing of Ascorbic Acid in Vivo. Anal. Chem. 2014, 86, 12206-12213. 52. Huang, P.; Wu, F.; Mao, L. Target-Triggered Switching on and off the Luminescence of Lanthanide Coordination Polymer Nanoparticles for Selective and Sensitive Sensing of Copper Ions in Rat Brain. Anal. Chem. 2015, 87, 6834-6841. 27



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

53. Wichterman, K. A.; Baue, A. E.; Chaudry, I. H. Sepsis and Septic Shock--A Review of Laboratory Models and a Proposal. J. Surg. Res. 1980, 29, 189-201.

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TOC

Microdialysis probe Brain dialysates

Cu2+ Aggregation

Silica coated CDs

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Tunable Fluorescent Silica-Coated Carbon Dots: A Synergistic Effect

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