Graphene Quantum Dots Wrapped Gold Nanoparticles with Integrated

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Graphene Quantum Dots Wrapped Gold Nanoparticles with Integrated Enhancement Mechanisms as Sensitive and Homogeneous Substrates for Surface-Enhanced Raman Spectroscopy Xuran Miao, Shengping Wen, Yu Su, Jiaju Fu, Xiaojun Luo, Ping Wu, Chenxin Cai, Raz Jelinek, Li-Ping Jiang, and Jun-Jie Zhu Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.9b01001 • Publication Date (Web): 07 May 2019 Downloaded from http://pubs.acs.org on May 8, 2019

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Analytical Chemistry

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Graphene Quantum Dots Wrapped Gold Nanoparticles with Integrated

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Enhancement Mechanisms as Sensitive and Homogeneous Substrates for

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Surface-Enhanced Raman Spectroscopy

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Xuran Miao†, Shengping Wen†, Yu Su†, Jiaju Fu†, Xiaojun Luo, Ping Wu‡, Chenxin Cai‡, Raz

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Jelinek§, Li-Ping Jiang*,†, and Jun-Jie Zhu*,†

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† State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and

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Chemical Engineering, Nanjing University, Nanjing 210023, China

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‡ Nanjing Normal University, Jiangsu Key Laboratory of New Power Batteries, College of

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Chemistry & Materials Science, Nanjing 210097, China

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§ Department of Chemistry, Ben Gurion University of the Negev, Beer Sheva 84105, Israel

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ABSTRACT

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Rational engineering of highly stable and Raman-active nanostructured substrates is still urgently

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demanded for achieving sensitive and reliable surface-enhanced Raman spectroscopy (SERS)

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analysis in solution phase. Herein, monodisperse N-doping graphene quantum dots wrapped Au

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nanoparticles (Au-NGQD NPs) were facilely prepared and further explored their applications as

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substrates in SERS-based detection and cellular imaging. The as-prepared Au-NGQD NPs

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exhibit superior long-term stability and biocompatibility, as well as large enhancement capability

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due to the integration of electromagnetic and chemical enhancements. The practical applicability

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of the Au-NGQD NPs was verified via the direct SERS tests of several kinds of aromatics in

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solution phase. Finite-difference time-domain (FDTD) simulations in combination with density

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functional theory (DFT) calculation were also successfully used to explain the enhancement

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mechanism. Furthermore, the Au-NGQD NPs were conjugated with 4-nitrobenzenethiol

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(4-NBT, as reporter) and 4-mercaptophenylboronic acid (MPBA, as targeting element) to

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construct the MPBA/4-NBT@Au-NGQD probes, which could specifically recognize glycan

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over-expressed cancer cells through SERS imaging on cell surface. The prepared Au-NGQDs

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show great potential as superior SERS substrates in solution phase for on-site Raman detection.

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As a powerful spectroscopic technique, SERS has spurred intense interests in various fields

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such as analytical chemistry and medical science due to its unique features of fingerprint

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specificity, multiplexing potential, and single-molecule-level sensitivity.1-4 Particularly, SERS

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can circumvent undesired fluorescence backgrounds arising from complex biomatrices, thereby

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presenting great promise in bioanalysis and imaging.5 Nanoparticles (NPs), as one kind of the

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most important SERS substrates, have wide applications in chemical and biological detection,

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labeling, and imaging due to their compatible size, richness in core–shell chemistry and structure

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dependent localized surface plasmon resonance properties.6-8 In particular, colloidal NP-based

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rapid onsite detection ranging from environment pollution to infectious diseases is in great need

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for human health and safety.2,9,10 However, for most solid substrates, the random absorption of

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target molecules might result in unreproducible SERS signals even if the solid substrates are

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well-fabricated. In contrast, monodispersed colloidal NP-based substrates can acquire more

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uniform signals in solution phase. However, their weak SERS enhancements limit their further

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applications in detecting targets at trace levels.11 Although NP assemblies such as dimers,12

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core-satellite structures13 and small clusters14 with high Raman effects have been used in the

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fabrication of SERS encoded probes, uncontrollable aggregation can result in the random

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distribution of hot spots with subsequent signal heterogeneity. Further, core-shell structures15,16

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have recently made great progress in dealing with signal homogeneity and good enhancing

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ability. Nevertheless, complicated fabrication procedures are usually required for most core-shell

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structures of SERS substrates. In addition, in many cases, several kinds of organic molecules

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without specific groups (e.g. -SH or -NH2) have low affinity toward the metal colloidal NPs, thus

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hindering their close contact with the electromagnetic “hot spots” to achieve the ultra-sensitive

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SERS detection. To address the concerns mentioned-above, much effort is still highly needed to

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construct the facilely-synthesized and universal metal nanohybrids with higher SERS

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enhancements. 3 ACS Paragon Plus Environment


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Graphene, a famous two-dimensional (2D) carbon nanomaterial, has captured notable

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attention in various promising applications such as energy storage,3 photocatalysis,17 and

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bioanalysis18 because of its fascinating optical, thermal, and electronic properties. Previous

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studies have proven that graphene can be employed as the planar substrate for Raman

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measurements due to the charge transfer-induced chemical mechanism (CM) enhancement.19,20

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Recently, higher Raman sensitivity has been reported in graphene/metallic NPs composite

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structures compared to the bare NPs.21,22 On one hand, the charge transfer between the molecules

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and graphene can enhance the Raman signals.23 On the other hand, the π-π staking between the

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graphene and absorbed molecules can shorten the distance between the molecules and the

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substrate which will further enhance the Raman signals due to the electrical mechanism (EM).24

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In addition, graphene also serves as a building block of an atomically flat SERS substrate where

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a much uniform Raman signal could be obtained.21 Compared to conventional graphene sheets,

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graphene quantum dots (GQDs) have larger specific surface areas and more accessible edges,

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which lead to a more effective adsorption of target molecules.25 They possess a higher

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enhancement factor than conventional graphene due to the existence of Van Hove singularities in

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the electronic density of states under given conditions.26 Therefore, it is anticipated that the

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GQD-metal nanoparticle composites might be an excellent SERS substrate to obtain uniform

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signals with high sensitivity. Several works reported the synthesis of GQD-metal nanoparticle

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composites,24,27-29 but most of them used multi-step construction methods which were complex

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and uncontrollable. Furthermore, many fabricating methods brought about a continuous

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graphene shell over the metal nanoparticle, with which only molecules having affinity to

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graphene in solution could be detected, limiting its universality in SERS detection.

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In this work, nitrogen-doped graphene quantum dots (NGQDs) wrapped Au nanoparticles

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were facilely synthesized, with the structure like a kind of Chinese traditional food named

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‘glutinous rice sesameballs’. Different from other multi-step fabrication method and reduction 4 ACS Paragon Plus Environment

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method, this facile method can effectively control the density of the wrapped NGQDs, leading to

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‘sesameballs’ textured Au-NGQD NPs. They show great mono-dispersity under the protection of

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cetyltrimethylammonium bromide (CTAB) and NGQDs. The prepared monodispersed

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Au-NGQD NPs possess the homogeneous distribution of the hot spots, resulting in the excellent

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signal uniformity, and breaking through the bottleneck of SERS in analytical chemistry for life

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science in which the signal uniformity is a long-term existing problem.30 The prepared

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Au-NGQD NPs can generate stronger, reproducible, and quantifiable SERS signals with a high

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enhancement factor (EF) up to 2.01×106 (Figure S1), hence, adsorbed molecules at an extreme

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low 1 pM could be detected in solution phase. The universality of Au-NGQD NPs in solution

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phase was also verified by testing several kinds of aromatics. These SERS reporter molecules

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including the benzenethiol molecules and dye molecules with large π conjugated structures.

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FDTD simulations along with DFT calculations were used to explain the enhancement

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mechanisms of Au-NGQD NPs. Importantly, Au-NGQD NPs were modified with

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4-mercaptophenylboronic acid (MPBA) and 4-nitrobenzenethiol (4-NBT) for glycan sensing

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applications on cell surface. Our results suggest that the MPBA/4-NBT co-modified Au-NGQD

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NPs (MN-Au-NGQDs) can selectively target glycans on cells and allow for distinguishing

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cancer cells from normal cells because of the glycan over-expression in cancer cells.

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EXPERIMENTAL SECTION

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Synthesis of monodisperse, quasi-spherical Au NPs with the size of 40 nm

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The synthesis of 40 nm monodisperse, quasi-spherical AuNPs was conducted as the previous

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report with some modifications. In detail, 2.0 mL of 0.1 M Tris solution was added into 48 mL

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of boiling water upon vigorous magnetic stirring. After refluxing for another 5 min, 0.5 mL of

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1% HAuCl4 and 0.5 mL of as-prepared colloidal Au seeds were quickly injected into the above

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reaction system, leading to rapid color changes from pink to powdery violet, and finally ruby red

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within 3 min. Then, the reaction solution was further kept for 15 min to warrant the formation of 5 ACS Paragon Plus Environment


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AuNPs. The resulting AuNPs solution was naturally cooled down, and subsequently stored at

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4 °C until use.

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Synthesis of Au-NGQDs

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Au-NGQDs were prepared using our established protocol with several modifications.31 In a

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typical synthesis, 20 mL of as-obtained AuNPs and 10 mL of 0.1 M CTAB solution were

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thoroughly mixed, and transferred to a 50-mL Teflon-lined autoclave. Then, the sealed autoclave

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was heated at 165 °C in an oven for 1 h. Afterwards, the system was allowed to cool down to

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room temperature. The as-synthesized Au-NGQDs were collected by centrifugation (10 min at

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6000 rpm), washed thrice with water, and dispersed in 20 mL of ultrapure water.

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Synthesis of MN-Au-NGQDs

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To prepare MN-Au-NGQDs, 1.0 mL of Au-NGQDs solution was incubated with 20 μL of

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ethanol containing MPBA (0.5 mM) and 4-NBT (0.5 mM) overnight under gently stirring. Next,

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the resultant solution centrifuged at 5000 rpm, and the obtained pellet was thereafter washed

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twice by ultrapure water, followed by resuspending to 1.0 mL of water.

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RESULTS AND DISCUSSION

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Characterizations of Au NPs and Au-NGQD NPs. The Au NPs of 40 nm were synthesized

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via the Tris-assisted seeded growth method with some modifications.32 TEM (Figure 1a) and

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SEM (Figure 1b) images exhibit that the prepared Au NPs have a uniform quasi-spherical shape

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with a narrow size distribution of about 40 nm. A high-resolution TEM (HR-TEM) image

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(Figure 1c) confirms that the as-synthesized Au NPs are single-crystalline, and the 0.233 nm

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lattice fringes corresponds to (111) planes of Au nanoparticle. The XRD pattern (Figure 1f)

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shows that the crystal facet of Au (111) is the major facet of the Au NPs, which matches well

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with the HR-TEM image. The Au-NGQD NPs were further synthesized in the presence of

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CTAB with a modified hydrothermal method.31 HR-TEM image and SAED pattern (Figure S2) 6 ACS Paragon Plus Environment

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demonstrate that the Tris-assisted synthesized Au NPs of 40 nm are stable enough to remain

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monodisperse with single crystalline structure under the protection of CTAB during the

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hydrothermal process, which can also be confirmed by UV-vis spectroscopy (Figure 1g). Figure

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1g displays that the spherical Au NPs present a strong localized surface plasmon resonance

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(LSPR) band at 526 nm, while almost no shift could be observed after the formation of

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Au-NGQDs, indicating no aggregation or morphology changes during the hydrothermal

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progress. HR-TEM and the inset (Figure 1d) show that the surfactant-converted NGQDs are

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exactly formed around the Au nanoparticles with a graphitic in-plane lattice space of 0.20 nm,

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which is consistent with the previous report.33 Besides, the well-matched TEM, STEM-HAADF

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images, and STEM-EDX elemental mapping image (Figure 1e) confirm that the NGQDs are

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indeed grown on the Au surface. The effect of the hydrothermal time on the morphologies of the

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as-prepared Au-NGQD NPs is also studied. It is found that the prepared Au-NGQD NPs changed

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from the ‘sesameballs’ texture to the core-shell structure with the extension of the hydrothermal

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time (Figure S3). When the reaction time was 0.5 h, nearly no change could see (Figure S3a).

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When the time was 1 h, the Au cores were covered by a discontinuous shell of NGQDs (Figure

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S3b), with partial Au surface exposed. While a thicker NGQD shell could be observed on the Au

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cores as the reaction time was prolonged up to 2 and 3 h (Figure S3c, d). All the above results

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indicate that monodisperse sesame balls-like Au-NGQD NPs have been successfully

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synthesized.



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Figure 1. Characterization of as-synthesized Au-NGQD NPs. (a) TEM image of Au NPs. (b)

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SEM image of Au NPs. (c) HR-TEM image of Au NPs. (d) HR-TEM image of Au-NGQD NPs.

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(e) TEM, STEM-HAADF, and Au, N, O, overlay elemental mapping of Au-NGQD NPs. (f)

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XRD pattern of Au NPs. (g) UV-visible spectra of Au NPs and Au-NGQDs. (Note that the

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Au-NGQDs used here are prepared at 1 h of hydrothermal time.)


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Figure 2. (a) SERS spectra of bulk 4-NBT, Au NPs, NGQDs and Au-NGQD NPs in solution.

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Raman-dye molecules (4-NBT) were added to the solution for direct detection. (b) SERS spectra

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of 4-NBT incubated with different colloidal NPs. (c) Multiple points Raman signal collection

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profiles of Au-NGQD NPs. (d) Raman-dye molecule concentration-dependent changes in SERS

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signal intensity with Au-NGQD NPs. All the spectra were acquired using a 50× telephoto

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objective at 633 nm excitation with the laser power of 17 mW and acquisition time of 10 s. The

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concentration of Au NPs and Au-NGQD NPs were both 100 pM, and the concentration of

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Raman molecule was 2.0 µM.

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SERS properties of Au-NGQD NPs. To assess the SERS effect of the Au-NGQD NPs, we

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collected Raman signals of 2.0 µM 4-NBT (as the reporter molecule) in the colloids of AuNPs

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(40 nm), NGQDs and Au-NGQD NPs. Note that AuNPs and Au-NGQD NPs have the same

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particle concentrations. NGQDs were prepared under the same conditions in the absence of Au

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NPs (Figure S4). All the colloids were tested in a homemade cell and were controlled under the

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same detection depth during every parallel Raman measurements. As seen in Figure 2a, the

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highest signal of 4-NBT is clearly observed in the colloidal Au-NGQDs solution compared with 9 ACS Paragon Plus Environment


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those in both bare AuNPs and NGQDs. The Raman bands at 1081, 1333, and 1570 cm−1 are the

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characteristic peaks of 4-NBT, corresponding to C-S stretching (νCS), O−N−O stretching (νNO2)

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and C−C stretching phenyl-ring (νCC), respectively. In contrast, no Raman signals could be

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detected from the bulk solution of 4-NBT (black curve, inset in Figure 2a). These results implied

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that the NGQDs wrapped on AuNPs can endow the Au-NGQD hybrids with exceptional SERS

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performance. Furthermore, we also compared the SERS activity of as-prepared Au-NGQD NPs

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with those of other monodisperse metal nanomaterials such as Au NPs (Figure 1a 40 nm), Au

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nano-stars (AuNSs) (Figure S5a 50 nm) and Ag NPs (Figure S5b 50 nm), under the same

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conditions, which are often used as good SERS substrates. Figure 2b demonstrates that the

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Raman intensities of 4-NBT are achieved as follows in aforesaid colloids: Au-NGQDs>> Au

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NSs ≈ Ag NPs > Au NPs. Specifically, the SERS signal from Au-NGQDs is approximately

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100-fold stronger than that from naked AuNPs of the same size. All above results reconfirm the

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excellent SERS effect of the Au-NGQDs substrate. In addition, the SERS response is relatively

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stable and uniform in the Au-NGQDs colloidal solution at different test points, with a relative

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standard deviation (RSD) at 1333 cm-1 of 5.5% (Figure 2c), showing the great superiority to

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solid Raman substrates in signal uniformity. For evaluating the batch-to-batch reproducibility,

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we further investigated the SERS spectra of 4-NBT on different batches of Au-NGQD NPs

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(Figure S6). The obtained RSD for Raman intensities at 1333 cm-1 is 4.4%, which suggests

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acceptable batch reproducibility for the Au-NGQD substrate. As we know, the colloidal stability

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of the Au-NGQD NPs is another issue that should be seriously considered for acquiring

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reproducible SERS signals. Experimental investigations (Figure S7a, b) demonstrate that no

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obvious change is observed in both UV-visible and SERS spectra for the Au-NGQD NPs during

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the shelf time of four months. Meanwhile, the Au-NGQD NPs have high salt tolerance even in

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the presence of 100 mM of NaCl, indicating their excellent colloidal stability (Figure S7c, d).

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The prepared Au-NGQD NPs were further applied as colloid substrate for sensitive and 10 ACS Paragon Plus Environment

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quantitative SERS analysis in solution. Figure 2d shows the concentration-dependent SERS

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profile of 4-NBT in the Au-NGQDs colloidal solution. As can been seen, 4-NBT with a much

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lower concentration (even down to 1 pM) can be sensitively detected using the as synthesized

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colloidal solution, without any salt addition for nanoparticle aggregation to induce

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electromagnetic “hot spots”. A linear calibration curve at the 1333 cm-1 band is

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I1333=449+4090logC (C: nM, R2 = 0.995) with the concentration range from 1 nM to 1µM. The

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RSD of 6% (C = 10 nM, n = 9) is achieved. Therefore, the proposed Au-NGQD colloid substrate

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might hold great promise for direct SERS detection of some important analytes in solution phase

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at trace level.

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Figure 3. Raman spectra of (a) DTNB, (b) MBN, (c) 4-NBT, (e) R6G, (f) RB, (g) CV on Au

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NPs (black line) and Au-NGQD NPs (red line), respectively. Comparison of Raman intensities

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obtained in Au NPs (blue column) and Au-NGQD NPs (red column) solutions: (d) molecules

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with thiol group and (h) dye molecules with large π conjugation with NGQDs. The

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corresponding Raman intensity was figured out by the dash line.

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The application potential of the Au-NGQD NPs in solution was tentatively expanded to the

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SERS detection of representative aromatic compounds, since some of them might pose

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unexpected health risks and environmental pollution after illegal abuse and arbitrary discharge. 11 ACS Paragon Plus Environment


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For this purpose, two groups of aromatic compounds were selected as the models in the

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subsequent SERS analysis. One group (group I) comprises molecules of small benzene rings

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with thiol groups (Insets of Figure 3a-c) such as 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB),

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4-mercaptobenzonitrile (MBN), and 4-NBT, while another group of aromatic dye molecules

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have large conjugated structures (group II) (Insets in Figure 3e-g) including rhodamine 6G

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(R6G), rhodamine B (RB), and crystal violet (CV). Generally, 2.0 µL of the analyte (100 µM)

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was respectively mixed with 98.0 µL of Au-NGQD NPs (0.2 nM), and then subjected to Raman

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tests. For the analytes in group I, the intensities of characteristic Raman peak are massively

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amplified in the Au-NGQD NPs solution while much weaker in the bare AuNP solution (Figure

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3a-c). The intensification for main peaks obtained in the Au-NGQD NPs solution relative to that

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in the AuNPs solution are calculated to be 10, 25, and 53-fold for MBN, DTNB, and 4-NBT

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(Figure 3d), respectively. The signals of other molecules in group I have also been enhanced to

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varying degrees, including 4-mercaptobenzoic acid (MBA), 4-mercaptophenylboronic acid

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(MPBA), and 4-aminothiophenol (PATP) (Figure S8). Similarly, for the analytes in group II, as

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compared to that in the AuNPs solution, the signals are greatly enhanced with Au-NGQD NPs

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substrate for R6G, RB, and CV (Figure 3e-f), whose corresponding signals are magnified up to

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32, 40, and 78 times (Figure 3h), respectively. Above results indicate the widespread

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applicability of the Au-NGQD NPs for SERS-based analysis of aromatics in aqueous solution.

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Interestingly, we found that the Raman intensity changed with the thickness of the NGQD shell.

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We compared Raman spectra of 4-NBT and CV in the Au-NGQD NPs synthesized at different

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hydrothermal time since we know that the thickness of the NGQD shell increases along with

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hydrothermal time (Figure S3). The results (Figure S9) indicate that SERS signals are the

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strongest at 1 h of hydrothermal time when NGQDs are discontinuously wrapped to Au NP

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surface. Previous reports illustrated that the substrate induced doping such as N doping and the

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chemisorption capability of the film with different thicknesses, might also contribute to the 12 ACS Paragon Plus Environment

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whole Raman enhancement.34,35 Therefore, the wide availability and remarkable Raman activity

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of the Au-NGQD NPs substrate are likely attributed to the incomplete shell of NGQDs on the

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Au-NGQD NPs. The discontinuous NGQDs layer on Au-NGQD NPs not only can absorb dye

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molecules which have large π conjugation with them but also facilitate the combination between

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the specific groups (e.g. -SH or -NH2) and naked Au sites, showing a widespread detection

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application in solution phase than Au NPs or NGQDs colloid. In short, the ‘glutinous rice

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sesameballs’ like Au-NGQDs we reported broke through the limited usage of nanoparticle

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substrate in solution, showing a bright future in on-site test and SERS analysis in homogenous

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solution.

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SERS Enhancement Mechanisms. Two widely accepted mechanisms for SERS are the

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electromagnetic mechanism (EM) and the chemical mechanism (CM).36 The EM is based on the

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enhancement of the local electromagnetic field upon resonance excitation of LSPR, which is

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roughly proportional to |E|4. The CM is based mainly upon a partially resonant charge transfer

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between the molecules and the substrate as well as a non-resonant chemical interaction between

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the ground state of the molecule and substrate.37 In this work, we take these two enhancement

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mechanisms into consideration.

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Figure 4. (a) Maximum electric field intensity (Emax/E0)2 at the Au/H2O interface of the

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Au-NGQD NPs as a function of the wavelength and the electric field distribution of the 13 ACS Paragon Plus Environment


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Au-NGQD NPs obtained at the wavelength of 633 nm (inset). (b) The calculated results for the

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extinction spectrum (black curve) and scattering cross sections (red curve) of Au-NGQD NPs.

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To simulate the electric filed intensity and distribution of the prepared Au-NGQD NPs,

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three-dimensional FDTD simulations were performed. We modelled the ‘ glutinous rice

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sesameballs’ nanostructure with lots of 2 nm circular NGQDs (0.35 nm in thickness) wrapping a

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40 nm of Au nano-core. The gaps between NGQDs were modelled to be 1 nm according to our

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TEM results. Regions of enhanced electric field are observed at the surface of the Au-NGQD

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NPs. Therefore, the Raman signal of molecules attached to or near the surface of Au NP is

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expected to be greatly enhanced. A new resonant mode located at 633 nm appeared after the Au

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cores were decorated by NGQDs (Figure 4a), which might correspond to the coulping between

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Au and NGQDs. The result matches well with the UV-vis we collected and the Raman excitation

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wavelength (Figure S10), implying a predicable SERS enhancement effect of the Au-NGQD

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NPs and a larger EF than Au NPs. The enhanced Raman signal of Au-NGQD NPs was evaluated

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by quantifying the maximum electric field intensity (Emax/E0)2 (Figure 4a ).38 The (Emax/E0)2 at

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the Au/H2O interface of the Au-NGQD NPs nanostructures was estimated to be 43, signifying

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that EM can contribute an enhancement of ~1849 according to the relation of 𝐺𝑆𝐸𝑅𝑆 =

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|𝐸𝑚𝑎𝑥/𝐸0|4, which is about 100 times larger than Au NPs. Here Emax is the maximum electric

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field intensity at the laser excitation wavelength (λL, 633 nm), and E0 is the amplitude of the

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incident field. For comparison, we also simulated the electric field distribution of Au NPs and

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Au-NGQDs at the laser excitation wavelengths of 550 and 633 nm, respectively (Figure S11). A

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higher electric intensity of Au-NGQDs at 633 nm than the others demonstrates its greater SERS

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effect again. As seen in Figure 4b, a larger cross-section band at 633 nm simulated by FDTD

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also corroborates the result. In summary, the FDTD simulations convinces the EM contribution.

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However, it could not account for the whole enhancement of Au-NGQDs, since the EF we

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calculated is 2.01×106 (Figure S1). Therefore, we speculate that the CM might also play an 14 ACS Paragon Plus Environment

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283


important role in the excellent enhancement of Au-NGQDs.

284 285

Figure 5. The proposed chemical enhancement mechanism of CV on different substrates. (a–c)

286

The ground state charge transfer between CV and Au, NGQDs (2 nm), andAu-NGQD NPs. The

287

electron states in the CV/Au-NGQD NPs (or NGQD) system, which have the possibility to

288

contribute to the SERS, are marked by orange shadows. (d) Energy level diagram and charge

289

transfer transitions in the CV/Au-NGQD NPs complex. μmol denotes the molecular transition.

290

μi−CT and μk−CT denote the charge transfer transitions from the molecular ground states |i⟩ to

291

Au-NGQD NPs and from Au-NGQD NPs to the molecular excited states |k⟩, respectively. (e)

292

The density of states (DOS) of Au, NGQDs NPs and Au-NGQD NPs near the Fermi levels. Side

293

views of the electron density difference isosurfaces for CV chemisorbed onto the Au111 (f) and

294

Au-NGQD NPs (g). Blue and red colors correspond to electron depletion and accumulation

295

regions, respectively. The arrows indicate the direction of electron transfer. 15 ACS Paragon Plus Environment


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296

To further investigate the CM mechanism, the DFT calculations of CV on Au NPs, NGQDs

297

and Au-NGQD NPs have been conducted (Figure 5a-c). Charge transfer occurs when molecules

298

contact to the substrates until an equilibrium is achieved, leading to re-alignment of the band

299

structure.26,34 In the CV/Au system, the highest occupied molecular orbital (HOMO) level of CV

300

is located near the Fermi level (at −2.47 eV), close to that of Au. Under laser irradiation, Raman

301

scattering is generated by three steps according to the Feynman diagram (Figure 5d), which are

302

excitation of the electron in the ground state by the incident light, coupling of the excited

303

electron to the phonon, and radiation of the scattered light when the electron relaxes back to the

304

ground state.21 Enhancing any step of the Feynman process can induce the enhancement of the

305

Raman signals. Moreover, the charge transfer leads to a higher polarizability, therefore the

306

displacement of charge density easily occurs under the external light excitation, which also

307

probably results in a higher Raman scattering cross-section. The increased cross-section further

308

brings about the enhancement of Raman signals. Due to the ground-state charge transfer between

309

Au and CV, the electrons near the HOMO in the CV/Au system (marked by orange shadow in

310

Figure 5a) have the possibility to contribute to the Raman scattering, thus more electrons are

311

involved in the Raman scattering process of CV, leading to enhancement of electron−phonon

312

coupling (the second step of the Feynman process).21 Compared with the Au NPs, the HOMO of

313

2 nm NGQD s(−3.97 eV) mismatches with the HOMO of CV (−2.47 eV), implying a low

314

efficiency of ground-state charge transfer (Figure 5b). However, the SERS effects on Au-NGQD

315

NPs originate from the charge transfer (CT), as illustrated in Figure 5c and 5d, the HOMO and

316

LUMO (lowest unoccupied molecular orbital) levels of CV probe are −2.47 and −0.48 eV,

317

respectively, and the Fermi level of Au-NGQDs is determined to be −1.48 eV by DFT

318

calculations. The CT from both the CV HOMO to the Au-NGQD NPs’ Fermi level and the

319

Au-NGQD NPs’ Fermi level to the CV LUMO in the coupled complex are responsible for the

320

total Raman enhancement,39,40 resulting from the broad charge transfer resonance energy range.41 16 ACS Paragon Plus Environment

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321

These resonances borrow the intensity from molecular transition through a vibronic coupling

322

Herzberg−Teller process, thus largely magnifying the polarization tensor of the probe. Moreover,

323

the nearly symmetrical match of the Au-NGQD NPs’ Fermi level to the molecular HOMO and

324

LUMO further facilitates the CT. In the large number of allowed energy states for CT in

325

Au-NGQD NPs (DOS near the Fermi level, see Figure 5e) further gives rise to the high charge

326

transition probabilities (w) according to the Fermi’s golden rule: wab =

327

and |b⟩ denote the initial and final states for the charge transition, ℏ is the reduced Planck

328

constant, M is the interaction operator of the two states, and gb is the DOS of the final state.

2𝜋 ℏ

|⟨b|M|a⟩|2gb, where |a⟩

329

Except for the charge transfer resonances, the molecular resonance at 633 nm excitation

330

augments the crosssection of probe Raman scattering as well.42 As demonstrated in Figure S10,

331

the the probe molecules show prominent SERS intensities at 633 nm excitation, while SERS

332

signals are very low under laser wavelengths of 488 and 785 nm. Molecular FL quenching is

333

another consequence of the large charge transfer in the analyte-Au-NGQD NPs system, as

334

illustrated in Figure 5d. In addition, the immense CM-driven Raman enhancement can be

335

investigated by Bader charge analysis based on DFT calculations( Figure 5f, g). The DFT results

336

show that the electron transfer from Au-NGQD NPs to CV is 0.927 e/molecule, while for the

337

CV/Au complex, the electron transfer is 0.804 e/molecule. The values of charge transfer reveal

338

that the coupling of CV-Au-NGQD NPs is much stronger than that of CV/Au, which agrees well

339

with our experiment results. It is worth noting that the charge transfer resonances are expected to

340

be largely enhanced when vibronically coupled with the molecular resonance, with the degree

341

highly relevant to the analyte-Au-NGQD NPs interaction. Usually, CM is considered to be a

342

secondary or even negligible factor in the total Raman enhancement in noble-metal-based SERS

343

substrates.43 In our demonstrated results, however, it has been indicated that the Raman

344

enhancement of Au-NGQDs added by CM that borrows the intensities from the dye molecular

345

resonance contributes a lot to the excellent levels of LOD and EF, shedding new light on the CM 17 ACS Paragon Plus Environment


Page 18 of 25

346

enabled SERS effect. The obove results also inspire us to construct new SERS nanotags with

347

intergrated EM and CM enhanments.

348 349

Scheme 1. Schematic diagram of cellular surface glycans SERS imaging

350 351

Figure 6. SERS images of single L02 cell, HeLa cell and MCF-7 cell (Left: bright field; Middle:

352

SERS mapping images based on the intensity of 1333 cm-1; Right: Merged images).

353

354

Glycan expression of different cell lines probed by SERS imaging. Encouraged by their

355

high Raman enhancements, great mono-dispersity ， good signal uniformity and long-term

356

stability, the Au-NGQD NPs were employed to construct Raman probes for bioimaging

357

applications. Sialic acid (SA), one of glycans expressed on cell membranes, is considered as a 18 ACS Paragon Plus Environment

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358

potential cancer biomarker, because its elevated expression level has a close correlation with

359

diverse tumors.44-46 Here, SA is chosen as the model biomarker in subsequent cellular SERS

360

imaging. MPBA and 4-NBT are used as glycan recognition unit and Raman reporter,

361

respectively, which can be grafted on the Au-NGQDs to obtain MN-Au-NGQD NPs via Au-S

362

bonding. It is reported that MPBA can specifically bind to C-8,9 diol of glycans at the

363

physiological pH of 7.4 through the strong esterification.47,48 Therefore, the glycan expression

364

levels on cell membrane can be profiled after the cells are incubated with the MN-Au-NGQDs

365

probes. Scheme 1 shows a fabrication scheme of the MN-Au-NGQDs probes for SERS imaging

366

of glycan on the cells.

367

To obtain the optimal Raman response of the MN-Au-NGQDs probes, the amounts of

368

MPBA and 4-NBT for probe construction were investigated. As demonstrated in Figure S12, the

369

strongest SERS signal of the probes is attained when the concentration of MPBA increases up to

370

10 µM. Due to the competitive relation between 4-NBT and MPBA, the concentration of 4-NBT

371

is also optimized to be 10 µM. Biocompatibility of Raman probes is another critical issue that

372

should be considered in bioimaging. Before performing Raman imaging of SA on the cells, the

373

cytotoxicity of the as-prepared MN-Au-NGQDs was evaluated using MTT assays. In this study,

374

three cell lines, MCF-7 (human breast cancer cell), HeLa (human epithelial cervical cancer cell),

375

and L02 (normal liver cell) cells as models were incubated in DMEM culture containing varied

376

concentrations of MN-Au-NGQDs. Figure S13 indicates that all the cells exhibit a viability of

377

~98% in the tested concentration range, suggesting an excellent cytocompatibility of the

378

prepared SERS probe.

379

The MN-Au-NGQDs probes were then applied to profile the SA expression on cell

380

membranes. The probe could be specifically captured by the SA-terminated glycans on the cell 19 ACS Paragon Plus Environment


Page 20 of 25

381

surface via the chemo selective covalent linkage between the boronic acid groups on the

382

MN-Au-NGQDs probe and the diol structure of the glycans. The specificity of these three probes

383

(MPBA@Au-NGQDs, 4-NBT@Au-NGQDs, and MN-Au-NGQDs) was compared for SERS

384

imaging of SA on MCF-7 cells. Before that, we got the picture without any probe addition. There

385

is no obvious signal in the images (Figure S14), showing a very low signal background of this

386

method. As shown in Figure S15, after incubation with the MPBA@Au-NGQDs probe or the

387

4-NBT@Au-NGQDs probe alone, SERS signals are negligible in these controls and almost the

388

same as that of MCF-7 cells alone. In contrast, the Raman intensity has a great increment while

389

incubating with MN-Au-NGQDs probes, confirming that MPBA and 4-NBT have a great

390

coordination in SA SERS imaging. The mentioned phenomenon could be explained by the

391

following reasons: On the one hand, MPBA can act as the active targeting molecule; on the other

392

hand, 4-NBT can serve as the Raman reporter with a higher Raman response than MPBA at the

393

same concentration. Furthermore, the incubation time of MCF-7 cells (as the model) cultured

394

with 0.1 nM of MN-Au-NGQDs probes was optimized as shown in Figure S16. As can be seen,

395

cellular SERS imaging in 1333 cm-1 channel shows increased brightness with the extended

396

incubation time, and 60 min is selected at which the SERS signal intensity reaches a plateau.

397

To validate the availability of the proposed strategy, we intended to use the

398

MN-Au-NGQDs probes for Raman profiling the SA expression level in different cell lines, such

399

as MCF-7, HeLa, and L02 cells. Prior to cellular Raman imaging, these cell lines were separately

400

cultured with 1.0 nM of MN-Au-NGQDs for 60 min (37 °C, 5% CO2). Figure 6 shows Raman

401

images of SA distribution on cell surfaces. It is found that the image of HeLa cells demonstrates

402

a bit stronger Raman signals than MCF-7 cells. As a control, the image of L02 cells

403

(SA-negative normal cells) displays much weaker signals compared with those of MCF-7 cells

404

and HeLa cells under the same conditions (Figure 6, upper panel). This is possibly due to the

405

high expressions of SA on MCF-7 and HeLa cells. The obtained results are consistent with 20 ACS Paragon Plus Environment

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406

previous reports,49 suggesting that our strategy is feasible for differentiating SA-overexpressing

407

cancer cells. Likewise, taking MCF-7 cell line as an example, we further estimated the

408

reproducibility of cellular SERS imaging under the same conditions. Figure S17 presents the

409

reproducible

410

MN-Au-NGQDs probe is reliable for Raman imaging of SA on cells. In addition, by real-time

411

SERS monitoring of the SA expression in drug treated-cells, we hope that the proposed SERS

412

protocol may provide a new alternative strategy for precise medicine and drug screening.

413

CONCLUSIONS

414

In summary, the monodisperse nitrogen hybridized graphene quantum dots wrapped Au

415

nanoparticles were facilely synthesized. The wrapped NGQDs are discontinuous, leading to a

416

‘glutinous rice sesame balls’ structured Au-NGQD NPs. The prepared Au-NGQD NPs show

417

great potential as SERS nanotags since they exhibit strong biological stability and extremely

418

uniform SERS signals in solution phase with large enhancement factor up to 2.01×106. They

419

show great SERS enhancement for most kinds of SERS reporter molecules in solution phase,

420

which display the wide application for on-site detection. The great SERS enhancement results

421

from the synergy of CM and EM verified by the FDTD simulations in combination with DFT

422

calculations. This study further developed a novel probe for sensitive SERS imaging of glycans

423

on living cells, thereby distinguishing the cancer cells from normal cells. The prepared ‘glutinous

424

rice sesame balls’ structured Au-NGQD NPs open a new avenue for highly reliable SERS onsite

425

detections in solution phase that show a bright future for SERS bioanalysis.

signals

between

different

batches

of

426 427 428

ASSOCIATED CONTENT 21 ACS Paragon Plus Environment

cellular

images.

Therefore,

the


Page 22 of 25

429

Supporting Information

430

The Supporting Information is available free of charge on the ACS Publications website.

431

Additional experimental section; Calculation of enhancement factor; Characterizations of

432

Au-NGQDs, NGQDs, Au nanostar, and Ag NPs; Raman reproducibility and colloidal stability of

433

Au-NGQDs; Raman tests of other aromatic molecules, Raman effect of Au-NGQDs synthesized

434

at different hydrothermal time; Selection of laser excitation; The electric field distribution of the

435

Au and Au-NGQD NPs; Optimization and toxicity test of MN-Au-NGQDs; Optimization of the

436

SERS mapping parameters; Reproducibility of mapping method.

437

AUTHOR INFORMATION

438

Corresponding Authors

439

* E-mail: [email protected], [email protected]

440

Author Contributions

441

Xuran Miao and Shengping Wen contributed equally to this work.

442

The manuscript was written through contributions of all authors. All authors have given approval

443

to the final version of the manuscript.

444

Notes

445

The authors declare no competing financial interest.

446

ACKNOWLEDGMENT

447

The authors greatly appreciate the financial support from the National Natural Science

448

Foundation of China (21775070) and the international cooperation foundation from Ministry of

449

Science and Technology (2016YFE0130100).

450

References 22 ACS Paragon Plus Environment

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(1) Qian, X. M.; Nie, S. M. Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications, Chem. Soc. Rev. 2008, 37, 912-920. (2) Gubala, V.; Harris, L. F.; Ricco, A. J.; Tan, M. X.; Williams, D. E. Point of Care Diagnostics: Status and Future, Anal. Chem. 2012, 84, 487-515. (3) Bonaccorso, F.; Colombo, L.; Yu, G.; Stoller, M.; Tozzini, V.; Andrea, C. Graphene, related two-dimensional crystals, and hybrid systems for energy conversion and storage, Science 2015, 347, 1246501. (4) Tian, L.; Tadepalli, S.; Fei, M.; Morrissey, J. J.; Kharasch, E. D.; Singamaneni, S. Off-Resonant Gold Superstructures as Ultrabright Minimally Invasive Surface-Enhanced Raman Scattering (SERS) Probes, Chem. Mat. 2015, 27, 5678-5684. (5) Jun, B. H.; Kim, G.; Mi, S. N.; Kang, H.; Kim, Y. K.; Cho, M. H.; Jeong, D. H.; Lee, Y. S. Surface-enhanced Raman scattering-active nanostructures and strategies for bioassays, Nanomedicine 2011, 6, 1463–1480. (6) Ma, Y.; Promthaveepong, K.; Li, N. Gold Superparticles Functionalized with Azobenzene Derivatives: SERS Nanotags with Strong Signals, ACS Appl. Mater. Interfaces 2017, 9, 10530. (7) Huang, C. W.; Hao, Y. W.; Nyagilo, J.; Dave, D. P.; Xu, L. F.; Sun, X. K. Porous Hollow Gold Nanoparticles for Cancer SERS Imaging, J. Nano Res. 2010, 10, 137-148. (8) Pinkhasova, P.; Puccio, B.; Chou, T.; Sukhishvili, S.; Du, H. Noble metal nanostructure both as a SERS nanotag and an analyte probe, Chem. Commun. 2012, 48, 9750. (9) Han, K. N.; Choi, J. S.; Kwon, J. Three-dimensional paper-based slip device for one-step point-of-care testing, Sci Rep 2016, 6, 25710. (10) Kim, J. H.; Park, J. E.; Lin, M.; Kim, S.; Kim, G. H.; Park, S.; Ko, G.; Nam, J. M. Sensitive, Quantitative Naked-Eye Biodetection with Polyhedral Cu Nanoshells, Adv. Mater. 2017, 29. (11) Lei, J.; Ju, H. Signal amplification using functional nanomaterials for biosensing, Chem. Soc. Rev. 2012, 41, 2122-2134. (12) Zhou, W.; Li, Q.; Liu, H.; Yang, J.; Liu, D. Building Electromagnetic Hot Spots in Living Cells via Target-Triggered Nanoparticle Dimerization, ACS Nano 2017, 11, 3532-3541. (13) Zhao, X.; Xu, L.; Sun, M.; Ma, W.; Wu, X.; Kuang, H.; Wang, L.; Xu, C. Gold-Quantum Dot Core-Satellite Assemblies for Lighting Up MicroRNA In Vitro and In Vivo, Small 2016, 12, 4662-4668. (14) Zhou, X.; Xu, W. L.; Wang, Y.; Kuang, Q.; Shi, Y. F.; Zhong, L.B.; Zhang, Q. Q. Fabrication of Cluster/Shell Fe3O4/Au Nanoparticles and Application in Protein Detection via a SERS Method, J. Phys. Chem. C 2010, 114, 19607–19613 (15) Kim, M.; Ko, S. M.; Kim, J. M.; Son, J.; Lee, C.; Rhim, W. K.; Nam, J. M. Dealloyed Intra-Nanogap Particles with Highly Robust, Quantifiable Surface-Enhanced Raman Scattering Signals for Biosensing and Bioimaging Applications, ACS Central Sci. 2018, 4, 277-287. (16) Shen, W.; Lin, X.; Jiang, C.; Li, C.; Lin, H.; Huang, J.; Wang, S.; Liu, G.; Yan, X.; Zhong, Q.; Ren, B. Reliable Quantitative SERS Analysis Facilitated by Core-Shell Nanoparticles with Embedded Internal Standards, Angew. Chem. Int. Edit. 2015, 54, 7308-7312. (17) Han, L.; Wang, P.; Dong, S. Progress in graphene-based photoactive nanocomposites as a promising class of photocatalyst, Nanoscale 2012, 4, 5814-5825. (18) Sun, Z.; Chang, H. Graphene and Graphene-like Two-Dimensional Materials in Photodetection: Mechanisms and Methodology, ACS Nano 2014, 8, 4133-4156. (19) Tan, P. H.; Han, W. P.; Zhao, W. J.; Wu, Z. H.; Chang, K.; Wang, H.; Wang, Y. F.; Bonini, N.; Marzari, N.; Pugno, N. The shear mode of multilayer graphene, Nat. Mater. 2012, 11, 294-300. (20) Lee, J. U.; Yoon, D.; Cheong, H. Estimation of Young's modulus of graphene by Raman spectroscopy, Nano Lett. 2012, 12, 4444. (21) Xu, W.; Ling, X.; Xiao, J.; Dresselhaus, M. S.; Kong, J.; Xu, H.; Liu, Z.; Zhang, J. Surface enhanced Raman



496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540

Page 24 of 25

spectroscopy on a flat graphene surface, Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 9281-9286. (22) Xie, L.; Ling, X.; Fang, Y.; Zhang, J.; Liu, Z. Graphene as a substrate to suppress fluorescence in resonance Raman spectroscopy, J. Am. Chem. Soc. 2009, 131, 9890-9891. (23) Jung, N.; Kim, N.; Jockusch, S.; Turro, N. J.; Kim, P.; Brus, L. Charge Transfer Chemical Doping of Few Layer Graphenes: Charge Distribution and Band Gap Formation, Nano Lett. 2009, 9, 4133-4137. (24) Wang, J.; Gao, X.; Sun, H.; Su, B.; Gao, C. Monodispersed graphene quantum dots encapsulated Ag nanoparticles for surface-enhanced Raman scattering, Mater. Lett. 2016, 162, 142-145. (25) Cheng, H.; Yang, Z.; Fan, Y.; Xie, X.; Qu, L.; Shi, G. Graphene-Quantum-Dot Assembled Nanotubes: A New Platform for Efficient Raman Enhancement, ACS Nano 2012, 6, 2237-2244. (26) Liu, D.; Chen, X.; Hu, Y.; Sun, T.; Song, Z.; Zheng, Y.; Cao, Y.; Cai, Z.; Cao, M.; Peng, L.; Huang, Y.; Du, L.; Yang, W.; Chen, G.; Wei, D.; Wee, A. T. S.; Wei, D. Raman enhancement on ultra-clean graphene quantum dots produced by quasi-equilibrium plasma-enhanced chemical vapor deposition, Nat. Commun. 2018, 9, 193. (27) Jin, J.; Zhu, S.; Song, Y.; Zhao, H.; Zhang, Z.; Guo, Y.; Li, J.; Song, W.; Yang, B.; Zhao, B. Precisely Controllable Core-Shell Ag@Carbon Dots Nanoparticles: Application to in Situ Super-Sensitive Monitoring of Catalytic Reactions, ACS Appl. Mater. Interfaces 2016. (28) Kim, Y. K.; Han, S. W.; Min, D. H. Graphene oxide sheath on Ag nanoparticle/graphene hybrid films as an antioxidative coating and enhancer of surface-enhanced Raman scattering, ACS Appl. Mater. Interfaces 2012, 4, 6545-6551. (29) Fei, X. X.; Liu, Z. M.; Li, Y; Yang, G. C.; Zhong, H. Q.; Zhuang, Z. F.; Guo, Z. Y. One-pot green synthesis of flower-liked Au NP@GQDs nanocomposites for surface-enhanced Raman scattering, J. Alloy. Compd. 2017, 725, 1084-1090. (30) Xu, W.; Ling, X.; Xiao, J.; Dresselhaus, M. S.; Kong, J.; Xu, H.; Liu, Z.; Zhang, J. Surface enhanced Raman spectroscopy on a flat graphene surface, PNAS 2012, 109, 9281-9286. (31) Fu, J.; Wang, Y.; Liu, J.; Huang, K. K.; Chen, Y.; Li, Y.; Zhu, J. J. Low Overpotential for Electrochemically Reducing CO2 to CO on Nitrogen-Doped Graphene Quantum Dots-Wrapped Single Crystalline Gold Nanoparticles, Acs Energy Letters 2018, 3. (32) Xia, H.; Xiahou, Y.; Zhang, P.; Ding, W.; Wang, D. Revitalizing the Frens Method To Synthesize Uniform, Quasi-Spherical Gold Nanoparticles with Deliberately Regulated Sizes from 2 to 330 nm, Langmuir 2016, 32, 5870-5880. (33) Zheng, X. T.; Ananthanarayanan, A.; Luo, K. Q.; Chen, P. Glowing graphene quantum dots and carbon dots: properties, syntheses, and biological applications, Small 2015, 11, 1620. (34) Tao, L.; Chen, K.; Chen, Z.; Cong, C.; Qiu, C.; Chen, J.; Wang, X.; Chen, H.; Yu, T.; Xie, W. 1T' transition metal telluride atomic layers for plasmon-free SERS at femtomolar levels, J. Am. Chem. Soc. 2018, 140, 8696. (35) Ling, X.; Wu, J.; Xie, L.; Zhang, J. Graphene-Thickness-Dependent Graphene-Enhanced Raman Scattering, J. Phys. Chem. C 2013, 117, 2369-2376. (36) Jensen, L.; Aikens, C. M.; Schatz, G. C. Electronic structure methods for studying surface-enhanced Raman scattering, Chem. Soc. Rev. 2008, 37, 1061. (37) Hao, Q.; Wang, B.; Bossard, J. A.; Kiraly, B.; Zeng, Y.; Chiang, I. K.; Jensen, L.; Werner, D. H.; Huang, T. J. Surface-Enhanced Raman Scattering Study on Graphene-Coated Metallic Nanostructure Substrates, J. Phys. Chem. C 2012, 116, 7249-7254. (38) Luo, X.; Liu, X.; Pei, Y.; Ling, Y.; Wu, P.; Cai, C. Leakage-free polypyrrole–Au nanostructures for combined Raman detection and photothermal cancer therapy, J. Mater. Chem. B 2017, 5, 7949-7962. (39) Lombardi, J. R.; Birke, R. L. A Unified Approach to Surface-Enhanced Raman Spectroscopy, J. Phys. Chem. C 2008, 112, 5605-5617. (40) Lombardi, J. R.; Birke, R. L. Theory of Surface-Enhanced Raman Scattering in Semiconductors, J. Phys.


Page 25 of 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

541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561


Chem. C 2014, 118, 11120-11130. (41) Shegai, T.; Vaskevich, A.; Rubinstein, I.; Haran, G. Raman Spectroelectrochemistry of Molecules within Individual Electromagnetic Hot Spots, J. Am. Chem. Soc. 2009, 131, 14390-14398. (42) Lasse Jensen, G. C. S. Resonance Raman Scattering of Rhodamine 6G as Calculated Using Time-Dependent Density Functional Theory, J. Phys. Chem. A 2006, 110, 5973-5977. (43) Morton, S. M.; Jensen, L. Understanding the molecule-surface chemical coupling in SERS, J. Am. Chem. Soc. 2009, 131, 4090-4098. (44) Fang, H.; Kaur, G.; Wang, B. Progress in boronic acid-based fluorescent glucose sensors, Chin. J. Org. Chem. 2007, 14, 481-489. (45) Tang, Y.; Yang, Q.; Wu, T.; Liu, L.; Ding, Y.; Yu, B. Fluorescence enhancement of cadmium selenide quantum dots assembled on silver nanoparticles and its application to glucose detection, Langmuir 2014, 30, 6324-6330. (46) Sun, X.; Stagon, S.; Huang, H.; Chen, J.; Lei, Y. Functionalized aligned silver nanorod arrays for glucose sensing through surface enhanced Raman scattering, RSC Adv. 2014, 4, 23382-23388. (47) Li, M.; Lin, N.; Huang, Z.; Du, L.; Altier, C.; Fang, H.; Wang, B. Selecting aptamers for a glycoprotein through the incorporation of the boronic acid moiety, J. Am. Chem. Soc. 2008, 130, 12636. (48) Xu, X. D.; Cheng, H.; Chen, W. H.; Cheng, S. X.; Zhuo, R. X.; Zhang, X. Z. In situ recognition of cell-surface glycans and targeted imaging of cancer cells, Sci Rep 2013, 3, 2679. (49) Zhang, X.; Chen, B.; He, M.; Zhang, Y.; Peng, L.; Hu, B. Boronic acid recognition based-gold nanoparticle-labeling strategy for the assay of sialic acid expression on cancer cell surface by inductively coupled plasma mass spectrometry, Analyst 2016, 141, 1286-1293.

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Graphene Quantum Dots Wrapped Gold Nanoparticles with Integrated

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