Core–Shell Regeneration Magnetic Molecularly Imprinted Polymers

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Core-shell Regeneration Magnetic Molecularly Imprinted Polymers-based SERS for Sibutramine Rapid Detection Zhigang Liu, Yan Gao, Li Jin, Hua Jin, Na Xu, Xiaoyang Yu, and Shihua Yu ACS Sustainable Chem. Eng., Just Accepted Manuscript • Publication Date (Web): 16 Apr 2019 Downloaded from http://pubs.acs.org on April 21, 2019

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Core-shell Regeneration Magnetic Molecularly Imprinted Polymers-based SERS for Sibutramine Rapid Detection Zhigang Liu,1 Yan Gao,1 Li Jin,2 Hua Jin,1Na Xu,3 Xiaoyang Yu,2 Shihua Yu*,2 1Centre

of Analysis and Measurement, Jilin Institute of Chemical Technology, Jilin,

132022 China. 2College

of Chemical & Pharmaceutical Engineering, Jilin Institute of Chemical

Technology, Jilin 132022 China. 3College

of Materials Science and Engineering, Jilin Institute of Chemical

Technology, Jilin 132022, China. *(Author for correspondence: e-mail: [email protected])

1

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ABSTRACT Molecularly imprinted polymers (MIPs) have the ability of predesigned specific recognition that can be selected to construct reliable functional materials. Combining the MIPs with magnetic nanoparticles, resulting in magnetic MIPs (MMIPs) which possess both facile manipulation and high selectivity. In this report, MMIPs microspheres are fabricated by coating a layer of MIPs on Fe3O4@Ag for SERS-based sensing of molecular species. The obtained Fe3O4@Ag@MIPs are further applied for simple, rapid, ultra-sensitive and label-free SERS detection of sibutramine (SIB, illegal additives), with a low LOD of 1.0×10-9 M. Moreover, the MMIPs microspheres exhibits ultra-high adsorption efficiency, selectivity, reusability, and good structural stability, which demonstrates the potential application for SERS. Particularly, the proposed approach of MMIPs-SERS can be successfully applied to quick screening of SIB in slimming supplements such as capsule, tea powder, tablet and the content is 6.18, 13.61, 3.09 mg·g-1, respectively. These properties make MMIPs microspheres a promising SERS substrate to detect the illegal additives in health-related products and chemical pollutants in the environment. KEYWARDS:SERS; MMIPs; repeatability; illegal additives; sibutramine INTRODUCTION Sibutramine (SIB) belongs to central appetite suppressants, which induces weight reduction by inhabiting appetite and stimulating energy expenditure and has been used as an anti-obesity drug in medicine.1-2 However, the Food and Drug Administration (FDA, US) recommended to stop using SIB in 2010. In the same year, 2

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the State Food and Drug Administration (SFDA, China) proposed a withdrawal of its production, sale and use in our country, owing to the increasing risk of cardiovascular disease and strokes. Whereas, some unscrupulous manufacturers still added SIB to the so-called natural slimming products illegally in recent years, seriously damaging the consumer's health.3-5 Therefore, it is urgent to establish a rapid, simple and ultra-sensitive method for selective detecting of SIB. At present, analysts have reported many methods for SIB screening, for example gas chromatography (GC),6 high performance liquid chromatography (HPLC),7 mass spectrometry (MS)8-9 etc. However, all of them need complex process for sample pretreatment or a certain amount of organic solvents, which cause some environmental problems and doesn't meet the requirement of green, sustainable chemistry although they belong to accurate detection methods. In the past decades, surface-enhanced Raman spectroscopy (SERS) has developed rapidly as a fast and ultra-sensitive tool for analytes detection in the fields of foods and biology.10-14 Molecularly imprinted polymers (MIPs) have properties of easy preparation, excellent reusability and high selectivity,

15-17

which make it is widely

applied to separate and enrich template molecules, including illegal, expensive and low solubility chemicals in various samples.18-19 Recently, some reports on using core-shell MIPs with SERS for enrichment, recognition, and detection of illegal additives or environmental pollutant have been demonstrated.20-21 Among them, Li’s research group22-25 has carried out a lot of work on SERS coupling molecular imprinting and achieved good results in selective detection of target, showing great 3

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potential for sample detection in simple matrix. However, in the complex sample system, the matrix will seriously interfere with the measurement results if the target compound or SERS substrate is not separated from the matrix efficiently after extraction. Undoubtedly, it will extend the application of SERS technology if the selective extraction, separation, and detection can be effectively integrated. Fe3O4 NPs show the characters of super paramagnetic and magnetic susceptibility, it can auxiliary separate of specific compounds after surface modification. Therefore, magnetic MIPs (MMIPs) would provide an efficient pretreatment tool with selectivity, simplicity and high adsorption capacity.26-27 To improve the affinity and selectivity of adsorption on noble metals for target molecules, we coated a layer of MIPs on the surface of Fe3O4@Ag by copolymerization, and SIB served as the template for MMIPs microspheres synthesis. As such, a combination of the MMIP-based extraction and SERS-based detection, is proposed in this work, which possesses the following merits: (1) The MMIPs-SERS has integrated sample pretreatment and rapid detection in one and used for qualitative screening of illegal additives. Compared with HPLC and MS, it is compatible with the concept of green chemistry without the need of complex pretreatment and toxic and harmful organic solvents. (2) The developed method is firstly used in the selective, fast and ultra-sensitive detection of SIB in health products. (3) Particularly, the MIPs is located in the outer layer of the magnetic particles, which avoids the oxidization process of AgNPs and preserved the nature of precious metals. Moreover, the probe molecules are isolated from MMIPs microspheres easily and could be regenerated by 4

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template extraction. In a word, SERS coupling with magnetic separation and molecular imprinting for the rapid detection of SIB conforms to the concept of green and sustainable chemistry. EXPERIMENTAL SECTION Chemicals and reagents. Acrylamide (AM), sodium acetate anhydrous, sibutramine hydrochloride, ethylene glycol, methacrylic acid (MAA), iron(III) chloride

hexahydrate,

ethylene

glycol

dimethacrylate

(EGDMA),

tetraethyl

orthosilicate (TEOS), 2,2’-azobis(isobutyronitrile) (AIBN), concentrated ammonium aqueous solution (25 wt%), sodium citrate, toluene and silver nitrite were purchased from Aladdin Reagent Co., Ltd. 31.6 mg standard SIB was firstly dissolved in 1 mL methanol, then it was diluted with ultrapure water to 10 mL and used as stock solution. Instruments and parameters. X-ray diffraction analysis were obtained on a D8 FOCUS (Bruker Germany). The images of the MMIPs were captured by a JSM-6700F scanning electron microscope and a JEM-2100F transmission electron microscope (JEOL, Japan). IR spectra date were taken from a FT-IR spectrometer (Perkin-Elmer, America). All Raman test were carried out by a portable optical fiber Raman spectrometer (BWTEK, Amercia) at excitation wavelength of 532 nm. HPLC date was analyzed by LC-20AB system (Shimadzu, Japan), chromatographic column was C18 (150 mm × 4.6 mm, 5 μm). The mobile phase consisted of ACN (A) and 0.1% formic acid (B), A: B = 1: 1. Under the condition of flow rate 1.0 mL/min, wavelength 223 nm, column temperature 25 °C and injection volume 20 μL. 5

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Synthesis of Fe3O4@Ag particles. (i) Fe3O4 magnetic microspheres were prepared by the modified solvothermal reduction approach.28 (ii) Then, Fe3O4 microspheres were functionalized with -NH2 (Fe3O4@SiO2-NH2) by surfactant-based sol-gel method according to our previous report.29 (iii) Locating AgNPs on Fe3O4@SiO2-NH2 surface via electrostatic interaction. Firstly, AgNPs were synthesized referring to the literature reported by Meisel and Lee.30 Then the freshly prepared AgNPs were mixed with Fe3O4@SiO2-NH2 to produce Fe3O4@Ag, the details of this work please to see our previous report.31-32 Preparation of MMIPs and MNIPs. (i) For functionalizing with vinyl double bonds, 50 mg Fe3O4@Ag was dispersed with ethanol-water solution (100 mL: 20 mL) in 150 mL round flask, and 50 µL AM was added in the mixture. After mechanical agitation for 30 min, AM adsorbs on Ag surface through the coordination reaction between Ag-N, then vinyl bonds functionalized nanoparticles (Fe3O4@Ag-C=C) were obtained.33 (ii) Fe3O4@Ag-C=C, SIB (0.1399 g, 0.5 mmol), 30 mL toluene, and 0.1727g MAA (2 mmol) were added into 50 mL conical flask, ultrasound for 15 min, then the mixture was pre-polymerized in dark for 12 h.19 (iii) Finally, the pre-polymerization and preassembly solutions were added into the three-necked flask (150 mL), to which AIBN (0.1089 g, 0.6 mmol), EGDMA (1.9810 g, 10 mmol) and toluene (40 mL) were added, and ultrasonic vibration for 15 min.34-35 The reactants was stirred at 65 °C for 5 h, then SIB Fe3O4@Ag@MIPs were rinsed three times with anhydrous ethanol, and the SIB removal from polymers by the eluent of methanol/acetic acid (9:1, v/v).21 After examining by UV-spectrometer at wavelength 6

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223 nm to validate the complete removal of SIB, the synthesized Fe3O4@Ag@MIPs (MMIPs) were dried in vacuum at 60 °C. In comparison, magnetic non-imprinted polymers (MNIPs, Fe3O4@Ag@NIPs) were synthesized in the same way without the addition of SIB as a blank in parallel. Regeneration experiments. In order to reduce the non-specific adsorption, the saturated Fe3O4@Ag@MIPs were first rinsed with acetonitrile after separated magnetically, then washed with methanol-acetic acid (9/1, V/V) for completing SIB desorption. Followed that, the regenerated Fe3O4@Ag@MIPs were reused as SIB adsorbent for the next analysis.36 Samples preparation. A total of 3 kinds of slimming supplements, including capsule (0.35 g × 60), tea powder (1 g × 10), and tablets (0.25 g × 24), were purchased from Internet. 0.1 g sample was dissolved with 5 mL 70% (v/v) methanol in a centrifuge tube, ultrasonically extracted for 10 min, and filtered through 0.45 μm membrane

filter,

then

collected

filtrate

for

further

analysis.

Meanwhile,

Fe3O4@Ag@MIPs (50 mg/mL, 50 μL) was added in the above filtrate and vortex mixed 5 min for thoroughly adsorption of SIB, then being separated and enriched by magnetic rack. Finally, SERS measurement of SIB was carried out by using a portable Raman spectrometer. RESULTS AND DISCUSSION Synthesis of SIB-MMIPs. The preparation procedure of SIB MMIPs by surface molecules polymerization technology is shown in Scheme. 1. As seen, (i) superparamagnetic Fe3O4 microspheres are firstly synthesized by solvothermal 7

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reaction as the magnetic core of MMIPs, making it is convenient to separate from test solution in the presence of external magnetic field. (ii) The as-prepared Fe3O4 particles are first functionalized with APTES and TEOS, which helps to form a layer of amine groups. Subsequently, the Fe3O4@SiO2-NH2 are mixed with AgNPs to produce Fe3O4@Ag. (iii) Under the reaction with AM, acrylamide vinyl groups are introduced onto the Fe3O4@Ag’s surface to induce the copolymerization of SIB with EDGMA. Then, the functional monomer MAA polymerizes with template molecule SIB on the surface of Fe3O4@Ag with the addition of AIBN. (iV) From it, MMIPs with surface imprinted cavities are obtained after removing template molecules. The release and recognition of templates are reversible, which is realized by eluting the MMIPs with methanol/acetic acid (9:1, (v/v)). SIB cannot be detected in the supernatant by UV, which indicates that the templates are fully removed from MMIPs. MNIPs are fabricated by the same procedure with MMIPs in the absence of SIB.

Ag

AM

(i)

(ii)

Fe3O4

Fe3O4@Ag

Fe3O4@Ag-C=C

N

Cl

Removing template (iV)

(iii)

Rebinding template

Fe3O4@Ag@MIPs

Fe3O4@Ag@MIPs-SIB

Scheme 1. Schematic diagram of the preparation process of Fe3O4@Ag@MIPs. 8

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Characterization of SIB-MMIPs. The morphologies of Fe3O4@SiO2, Fe3O4@Ag and MMIPs microspheres are shown in SEM and TEM images. Figure 1A shows that Fe3O4@SiO2 microspheres with diameter around 600 nm are successfully prepared. From Figure 1B, the core-shell structure of Fe3O4@Ag particle is obtained by aggregating AgNPs on the surface of Fe3O4@SiO2. After imprinting process, a thin polymer film is added to the Fe3O4@Ag to form core-shelled MMIPs (Figure 1C). The corresponding TEM image of a MMIPs microsphere (Figure 1D) shows that the Fe3O4@Ag core is fully coated by the polymer layer (gray color). The polymer layer has a thickness between 10 and 30 nm. According to the classical distance-dependent SERS mechanism, the shell with the thinner thickness has the higher SERS enhancement.37-38 As reported by Li and co-workers, the thickness of MIPs layer in the range of 2-40 nm can enhance the Raman signal, which may result from “gate effect’’.22-25

A

B

B

C D

10 nm

50 nm 50

nm

Figure 1. SEM images of Fe3O4@SiO2 (A), Fe3O4@Ag (B), Fe3O4@Ag@MIPs (C), 9

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and TEM image of Fe3O4@Ag@MIPs (D).

In the FT-IR spectra (Figure 2A), the band at 580 cm-1 indicates the stretch of Fe-O.39 In the meantime, the absorption peaks are near 800 cm−1 and 1096 cm−1 could be assigned to the stretch of Si-O-Si and Si-O.40 And the declining peak intensity of Fe-O and Si-O-Si in Fe3O4@Ag demonstrates that the successful aggregations of AgNPs onto the Fe3O4@SiO2. In addition, a new peak at 1720 cm-1 is attributed to the C=O vibration of EGDMA confirms that the MIPs is wrapped on the surface of Fe3O4@Ag successfully.41-42 There is no difference in absorption peaks between MMIPs and MNIPs, suggesting the leakage of templates can be ignored. Figure 2B presents the XRD patterns of the magnetic nanoparticles and MMIPs. The presence of crystalline structure of the magnetite proves that all the products are composed of Fe3O4. However, the peak intensity of Fe3O4 decreases after coating SiO2, AgNPs and MIPs shells, indicating the polymerization reaction did not destroyed the crystalline structure. In the case of Fe3O4@Ag, four new diffraction peaks marked with “※” are ascribed to (111), (200), (220), and (311) crystal planes of Ag, respectively, demonstrating the SERS active silver nanoparticles are successfully assembled on Fe3O4@SiO2 surface.43 Furthermore, the peak intensity of MMIPs has reduced obviously reveals that the Fe3O4@Ag is successfully coated by imprinted polymers in the precipitation polymerization process.

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A

Fe3O4@Ag@NIPs

※—Ag

Intensity (a.u.)

Fe3O4@Ag@MIPs 1720

Fe3O4@Ag Fe3O4@SiO2 Fe3O4

4000

2000

1000



※ □



□※



Fe3O4@Ag@MIPs Fe3O4@Ag

Fe3O4@SiO2 Fe3O4

580

3000

B



□—Fe3O4 □

T%

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

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10

20

30

40

50

60

70

80

2 ()

-1

Wavenumber (cm )

Figure 2. (A) FT-IR spectra and (B) XRD pattern of magnetic nanoparticles and MMIPs. Analytical performance of MMIPs. The prepared MMIPs is used as SERS-active substrate for the detection of SIB at different concentrations. As seen from Figure 3A, the observed Raman bands from 600 to 1600 cm-1 are ascribed to the signals of SIB, which locate at 880 cm-1 (γ(=C-H)(p-substituted phenyl ring)), 1094 cm-1 (νC2-N1-C8), 1468 cm-1 (ν(C-C)(phenyl ring) + δ(CH3)), and 1593 cm-1 (ν(C-C)(phenyl ring)). It shows that the peak intensity declines with the decrease of SIB concentration. However, the Raman feature peaks of SIB can be observed clearly even at the low concentration of 10−9 M. Figure 3B reflects the linearity between concentrations of SIB and SERS intensity at 1468 cm-1. Based on the above results indicate that the as-prepared MMIPs can be explored for the trace detection of SIB. Comparing to other reported approaches for SIB identification (see Supporting Information, Table S1), the developed method presents significant advantages in fast and ultra-sensitive detection.

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7000

A

6000

1468 1.010 M

1094

Equat i on

y = a + b* x

Wei ght

I nst r ument al

Resi dual Sum of Squar es

1. 74613

Adj . R- Squar e

0. 99834

B Val ue

-5

Intensity (a.u.)

Intensity (a.u.)

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

-6

1.010 M -7

1.010 M -8 1.010 M -9

1.010 M blank

5000

I nt er cept B

Sl ope

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St andar d Er r or

14573. 60315

284. 56398

1592. 22155

32. 48113

4000 3000 2000 1000 0

600 800 1000 1200 1400 1600 1800 2000 2200 2400

-9

-8

-1

Raman Shift (cm )

-7

-6

-5

logCanalyte

Figure 3. (A) SERS spectra of SIB adsorbed on Fe3O4@Ag@MIPs, (B) The calibration curve of SIB concentrations versus Raman intensity at 1468 cm-1. Competitive binding of SIB using MMIP and MNIP. In order to prove that the effective

signal

is

generated

from

specific

binding

of

SIB

to

the

Fe3O4@Ag@MIPs, we also test Fe3O4@Ag@NIPs to research its response to different concentrations of SIB. Figure 4A and Figure 4B illustrate the Fe3O4@Ag@MIPs produces much stronger signal due to the advantage of high binding sites for SIB.44-45 For investigating the binding performances of the MIP-coated and NIP-coated magnetic substrate, the adsorption kinetics experiment is performed using 50 µg/mL of SIB. From Figure 4C the MMIPs exhibits a rapid adsorption rate and reaches equilibrium in 5 min. Furthermore, the adsorption capacity of the MMIPs is far larger than that of the MNIPs. This indicates that a great deal of specific imprinted cavities produced in the process of MMIPs preparation after templates removal.46 Therefore, such an ideal adsorption material of MMIPs shows a high selectivity towards SIB.

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8000

A

B

7000

Fe3O4@Ag@MIPs

Fe3O4@Ag@MIPs Fe3O4@Ag@NIPs

6000

Intensity (a.u.)

Fe3O4@Ag@NIPs

Intensity (a.u.)

5000 4000 3000 2000 1000

60

1.

0

10

-4

-5

10 0 1.

10 0 1.

10 0

-6

-7

-8

1.

1.

10

2500

0

2000 -1

Raman Shift (cm )

1.

1500

10

1000

0

500

-9

0

Consentration (M)

C MMIPs

50 40

q (mg/g)

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

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30 20 10

MNIPs

0 0

10

20

30

40

50

60

Time (min)

Figure 4. (A) SERS spectrum of SIB (1.0×10-5 M) collected from MMIPs and MNIPs. (B) The variations of Raman intensity at 1468 cm-1 with different concentrations of SIB on two substrates. (C) The adsorption kinetics of MMIPs and MNIPs. Comparison of Fe3O4@Ag@MIPs with Fe3O4@MIPs@Ag. To evaluate the SERS activity of MIP-coated substrate and MIP-filling substrate, SIB is selected as probe molecules to complete a comparative experiment. After saturated adsorption for 10 min, the SERS spectra acquired from the above two substrates are shown in Figure 5A. As observed from the spectra, both them can detect SIB signals, but the intensity at 1468 cm-1 in SERS spectrum on Fe3O4@Ag@MIPs is several times larger than that obtained on Fe3O4@MIPs@Ag. The fact that the MIP-coated substrate gives more clear SERS signal, provides strong evidence that the MIPs layer with imprinted 13

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cavities on the surface of composite is beneficial to concentrate more target molecules to rebind to substrate.47 In addition, to investigate the reusability of two kinds of substrates, we try to regenerate the sensing surface by extraction of template with methanol-acetic acid (9/1, V/V), and contrast empirical results are presented in Figure 5B. It illustrates that the adsorption capacity of Fe3O4@Ag@MIPs begins to decrease slightly after washing for 5 times, which is mainly due to the partial destruction of imprinted cavity. However, the recognition cavities in polymer layer of Fe3O4@MIPs@Ag are in the sandwich of composite particles, which may be unfavorable to the entry and exit of template molecules.48 As a result, the adsorption and reusability capabilities of Fe3O4@MIPs@Ag are relatively weaker. Based on the above analysis, it is confirmed that Fe3O4@Ag@MIPs not only possesses the function of detection but also has the property of excellent reusability as a SERS sensor, laying the foundation for the practical application. 4000

A

Fe3O4@MIPs@Ag

3500

Fe3O4@Ag@MIPs

3000

Intensity (a.u.)

Intensity (a.u.)

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

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B

Fe3O4@Ag@MIPs Fe3O4@MIPs@Ag

2500 2000 1500 1000 500

500

1000

1500

2000

0

2500

1

-1

Raman Shift (cm )

2

3

4

5

6

7

8

9

10

Reused times

Figure 5. Reusability of Fe3O4@Ag@MIPs and Fe3O4@MIPs@Ag. (A) SERS spectra measured from SIB solution at the same concentration of 1.0×10−6 M and (B) adsorption-desorption cycle number. Furthermore, the SERS spectrum of MIP-coated substrate used for 2 cycles of 14

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reusability experiment is shown in Figure S1 in the Supporting Information. As can be seen, SIB is eluted from the MMIPs surface after the bound and the Raman band has disappeared. While these bands appear again after the regenerated MMIPs being dispersed in SIB solution. After two cycles, the MMIPs surface still exhibits the same signal strength, indicating that the MIPs layer are firmly assembled on Fe3O4@Ag surface and retain the original specific binding.50-51 Therefore, the prepared SERS substrate shows excellent regeneration capability. Reproducibility and stability of MMIPs. To test the reproducibility and stability of the MMIPs, ten sensors are fabricated independently under the same conditions and stored by refrigerated storage at 4 °C. The SERS spectra are collected from MMIPs stored for 0 to 10 months, and the results are shown in Figure S2A and visual description illustrated in Figure S2B, Supporting Information. SERS spectra for ten sensors present good reproducibility after storage for 10 months, which suggests that the MMIPs sensor possesses acceptable storage stability. These detailed investigations reveal that the Fe3O4@Ag@MIPs owns favorable reproducibility and stability. Applications. To test the applicability of the prepared sensor, it is applied to detect SIB in different commercial samples, including capsule, tea powder and tablet, which are claimed to be natural weight-losing produces without any illegal additives. The testing results are portrayed in Table 1. Three samples are detected as adulterants positive (Figure 6), and the content of SIB is 6.18, 13.61, 3.09 mg·g-1, respectively. In order to prove the validity of the results, SIB detection by HPLC (Figure S3, Supporting Information) is also performed for 15

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these samples. The results obtained based on the two methods are in high consistence, demonstrating such a fast screening technology with convenient operation, high selectivity, reusability. All together make it potential in monitoring of synthetic adulterants on-situ. Capsule Tea powder Tablet

Intensity (a.u.)

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

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500

1000

1500

2000

2500

3000

3500

-1

Raman Shift (cm ) Figure 6. SERS spectra of SIB residue in capsule, tea powder and tablet. Table 1. Application of the SERS and HPLC method in monitoring SIB in slimming supplements. Detected by SERS

Detected by

Consistence

(mg·g-1)

HPLC (mg·g-1)

(%)

capsule

6.18

6.92

89.31

tea powder

13.61

14.83

91.77

tablet

3.09

3.68

83.97

Samples

CONCLUSION In conclusion, we have successfully designed a novel chemical sensor (Fe3O4@Ag@MIPs, MMIPs), and combined use of MMIPs microspheres and SERS 16

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for the firstly measurement of trace amount SIB in slimming drug. The Fe3O4@Ag@MIPs are proved to possess the capability of rapid, efficient, selective and ultra-sensitive binding of SIB. Moreover, MMIPs has the characteristics of reusability, integration of pretreatment and detection in one, these properties make it conforms to the concept of green sustainable chemistry. Specially, the proposed technique is successfully applied in identification of SIB being illegal additives in slimming supplements, including capsule, tea powder and tablet and the content is 6.18, 13.61, 3.09 mg·g-1, respectively. Therefore, the MMIPs-SERS will become a potential technology for screening the trace level banned chemicals in the fields of foods, health-care products and cosmetics. AUTHOR INFORMATION Corresponding Author * E-mail: [email protected]. Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS We thank the financial support from the program of Jilin Department of Science and Technology (No. 20180520161JH) and Natural Science Foundation of Jilin Province (No. 20180101292JC). REFERENCES (1)

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TOC Graphic

A reusable MMIPs-based SERS substrate that integrates pretreatment and detection in one, and can be applied for rapid screening of sibutramine in slimming products.

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