Ju Yang*ab and
Sishi Leia
aChongqing Forensic Scientific Key Laboratory for Higher Education, Criminal Investigation School, Southwest University of Political Science and Law, Chongqing 401120, China. E-mail: yangjuzhb@163.com
bEngineering Research Center of Ministry of Education for Intelligent Justice, Chongqing 401120, China
First published on 22nd July 2025
In this study, a dual-mode sensing technique based on zeolitic imidazolate framework-8 (ZIF-8) and silver nanoparticle (Ag NP) composites is proposed to achieve visual primary screening and precise confirmation of illicit drugs by integrating the synergistic effect of colorimetric analysis and surface-enhanced Raman scattering (SERS) techniques. Ag NPs were loaded on the surface of ZIF-8 using an in situ synthesis strategy, and nanocomposites with dual enhancements of molecular enrichment and signaling were successfully constructed. The experiments showed that ZIF-8, with its high specific surface area and ordered porous structure, could efficiently adsorb illicit drug molecules. Meanwhile, Ag NPs, acting as a bifunctional active center, enabled the visual primary screening of illicit drugs via chromogenic reactions. Additionally, by utilizing the local surface plasmon resonance (LSPR) effect, Ag NPs formed nanoscale SERS hotspots, enhancing Raman signals for precise trace detection. The method achieves fast and accurate identification of heroin (HER), methamphetamine (MET) and etomidate (ETO). The multimodal sensing array effectively overcomes the limitations of traditional single detection methods in terms of timeliness, sensitivity and field applicability, providing a new idea for multimodal illicit drug detection.
In recent years, metal–organic framework (MOF) materials have shown great promise for application in illicit drug detection due to their high specific surface area, structural tunability and good potential for surface functionalization. For example, Au–Ag nanoparticle-modified cobalt-based MOF (Co-MOF) biosensors have improved the electrochemical detection of morphine;3 fluorescent nanoprobes based on Au NPs and UiO-66 composite nanomaterials have improved the sensitivity of morphine detection in blood samples;4 and a new type of fluorescent europium metal–organic framework (Eu-MOFs) synthesized by a one-step solvothermal method has provided an effective ‘signal-off’ platform for the rapid detection of methcathinone.5 However, the existing MOF-based sensing methods generally have the defects of single detection mode and lack of cost-effectiveness, which makes it difficult for them to meet the comprehensive needs of simplicity, rapidity and accuracy in field application scenarios. Colorimetric methods provide rapid initial screening through intuitive color changes,6 while SERS technology provides confirmatory analysis with its molecular fingerprinting capability (detection limits up to the picomolar level).7 In this system, silver nanoparticles (Ag NPs) exhibit dual advantages in colorimetric chromatography and SERS signal amplification due to their catalytic activity and significant local surface plasmon resonance (LSPR) effect, and their refractive index sensitivity is better than that of gold nanoparticles.8 However, the high surface energy of Ag NPs leads to the problem of oxidative agglomeration, which seriously limits their practical applications.9
To address this bottleneck, researchers attempted to complex Ag NPs with different carriers to improve dispersion and stability. For example, the Fe3O4/GO/Ag microspheres constructed by He et al. achieved multifunctional integration of SERS detection, catalytic degradation, and magnetic separation;10 Luo et al. constructed CNC/ZIF-8/Ag nanostructures using rigid nanofibrillated cellulose, which enhanced the ordered arrangement of Ag particles and SERS ‘hot spot’ uniformity.11 The Ni(OH)2/Ag composites prepared by Wen et al. were made by in situ deposition of Ag nanoparticles on the surface of Ni(OH)2 microspheres, which further enhanced the detection performance of the materials.12 However, the structures of the above prepared composite nanomaterials are complex, involving multilayer composites of multiple molecular materials, and this complex structure leads to a cumbersome preparation process, which is not conducive to large-scale and low-cost production, and the stability of the materials may be affected in multiple recycling. Recent cutting-edge materials, such as hydrophobic CuO@Ag nanowires, achieved quantitative SERS detection of 50 nm nanoplastics through the coffee ring effect;13 Ag/graphene/BaTiO3 composite substrates enhanced the SERS sensitivity by using a pyroelectric field to drive charge transfer.14 All of these novel nanostructured materials have demonstrated good detection sensitivity, but the challenges of simplicity, stability, and cost have yet to be overcome.
In contrast, ZIF-8, as a typical MOF material, in addition to the advantages of high specific surface area, controllable pore size, and easy synthesis of traditional metal–organic frameworks, has abundant imidazole groups in its skeleton that can form a strong coordination with Ag+ ions, promote the uniform in situ loading of Ag nanoparticles, effectively inhibit the agglomeration and oxidation of Ag NPs, and significantly enhance the material's stability and reusability.15 Meanwhile, the porous structure of ZIF-8 is conducive to the efficient enrichment of target drug molecules, which enhances the detection signal strength and improves the detection sensitivity. Therefore, ZIF-8 is an ideal carrier substrate for stable loading of Ag nanoparticles.
Based on this, this study proposes a ‘structural simplicity’ strategy based on the metal–organic framework ZIF-8 carrier and prepares ZIF-8/Ag composites by chemical reduction to achieve efficient synergy between the molecular enrichment function of ZIF-8 and the LSPR effect of Ag NPs, constructing a bimodal sensing platform for ZIF-8/Ag composites to achieve ‘colourimetric primary screening – SERS confirmation’ bimodal detection. This method achieves the colorimetric-Raman dual-mode recognition of heroin, methamphetamine and etomidate, providing a rapid and accurate technical means for on-site drug detection, which is of great practical significance for the innovation of anti-drug supervision technology.
The samples were synthesized using a PS-08A ultrasonic cleaner (Dongguan Jiekang Ultrasonic Equipment Co., Ltd., China), an FA1004 electronic analytical balance (Shanghai Shunyu Hengping Scientific Instrument Co., Ltd., China), an HMS-4G magnetic stirrer (Shanghai HUYI Industry Co., Ltd., China), a TG-16 high-speed centrifuge (Sichuan Shuke Instrument Co., Ltd., China) and a DZF-1B vacuum drying oven (Shanghai Longyue Instrument Co., Ltd., China). Raman spectra were measured using a DXR2 Raman spectrometer (Thermo Fisher Scientific, USA), UV-visible spectra were measured using a Specord 200 plus (Analytik Jena Analytical Instruments AG, Germany), and Fourier Transform Infrared spectra (FTIR) were measured using a LUMOS II micro-infrared spectrometer (BRUKER Inc., USA). Scanning electron microscopy (SEM) was conducted using an SU8600 ultra-high resolution scanning electron microscope (Hitachi, Japan), and X-ray photoelectron spectroscopy (XPS) was conducted using an ESCALAB multifunctional X-ray photoelectron spectrometer (Thermo Fisher Scientific Ltd., UK). The water used for the experiments was ultrapure water (Eco Exceed-Dc-60 water purifier, China).
The synthesis of ZIF-8/Ag was carried out as follows: first, 0.0165 g of ZIF-8 was dissolved into 20 mL of an aqueous solution and sonicated for 30 min. 5 mL of silver nitrate solution (0.023 M) was added to the homogeneously dispersed ZIF-8 suspension and stirred for 1 h at 800 rpm. Subsequently, 0.0321 g of trisodium citrate was dissolved into 5 mL of the aqueous solution and was added to the above solution and stirred for 5 min. Finally, 0.2 mL of sodium borohydride solution (0.002 M) was added drop by drop to the mixed solution and stirred for 5 min, and the resulting solution was centrifuged and re-dispersed in aqueous solution after 24 h of resting time to obtain a yellow solution (protected from light throughout).
0.2 mL of heroin, methamphetamine and etomidate were added to 0.2 mL of ZIF-8/Ag solution, respectively, and the solutions were sonicated for 3 min to homogenize the solutions to obtain the respective mixtures. The color changes of the solutions were directly observed by taking photographs of the color changes of heroin, methamphetamine and etomidate between the concentrations of 0.001 mg mL−1 and 1 mg mL−1, respectively, using a digital camera. Absorbance changes between 350 and 800 nm were recorded for the three mixtures using a UV-Vis spectrometer.
In order to demonstrate the reproducibility and sensitivity of the SERS assay, seven concentrations of each mixture were measured separately using the given parameters, and the corresponding SERS spectrograms were obtained and linearly fitted. To demonstrate the stability and homogeneity of the SERS method detection, a heroin mixture of 0.1 mg mL−1 was selected for SERS repeated measurements, and 30 sets of spectra were collected consecutively at the same substrate (30 s intervals) and analyzed for relative standard deviation.
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Fig. 1 SEM images of (a) ZIF-8 and (b) ZIF-8@Ag; element mapping of (c) Ag element, (d) C element, and (e) N element. |
Fig. 2(a) shows the XPS spectra of the materials ZIF-8 and ZIF-8/Ag. The XPS analysis provides the chemical constituent ions and bound states on the surface of the nanoparticles, and the characteristic peaks of all the constituent elements in ZIF-8/Ag can be clearly identified.19 In the Zn 2p spectrum of ZIF-8, the peaks of Zn 2p3/2 and Zn 2p1/2 were at 1022.1 eV and 1045.2 eV, respectively, which indicated the presence of the divalent state of zinc in ZIF-8 (Fig. 2(b)), and the peaks of the N 1s spectrum were –NH– (399.35 eV) and CN (400.4 eV), respectively (Fig. 2(c)). After loading Ag NPs, the positions of Zn 2p3/2 and Zn 2p1/2 were located at 1022.03 eV and 1045.3 eV, respectively (Fig. 2(d)), and the fitted peaks of N 1s appeared at 398.62 eV, which were generated due to the N–H and N–C bonds of imidazole (Fig. 2(e)). After the ion exchange and chemical reduction process, there were obvious Ag-related peaks in the ZIF-8/Ag sample, and the two characteristic peaks at 375.03 eV and 368.93 eV were the signal diffraction peaks of Ag 3d3/2 and Ag 3d5/2, respectively (Fig. 2(f)), which indicated that the Ag nanoparticles were successfully doped into the framework of ZIF-8. The XPS results indicated that the Ag nanoparticles had been successfully loaded into ZIF-8, which is consistent with the SEM results.
The FTIR spectra of ZIF-8 and ZIF-8/Ag are shown in Fig. 3, and the peak appearing at 1578 cm−1 corresponds to the CN stretching vibration, the peak at 1419 cm−1 is related to the ring stretching vibration, the peak at 2940 cm−1 corresponds to the stretching vibration of the exocyclic methyl-saturated C–H, and the peak at 3129 cm−1 corresponds to the stretching vibration of the intracyclic unsaturated C–H. The peaks of ZIF-8/Ag in the spectrograms are basically consistent with those of ZIF-8, indicating that Ag nanoparticles have been loaded on the surface of ZIF-8 and do not destroy the surface groups of ZIF-8.20
In the colorimetric assay based on ZIF-8/Ag nanocomposites, the solution color change showed a significant correlation with the illicit drug concentration and molecular structure (Fig. 4(a)–(c)). For HER, as the concentration gradually increased from 0.001 mg mL−1 to 1 mg mL−1, the solution color showed a continuous gradient: at a concentration of 0.001–0.01 mg mL−1, the color deepened from light yellow to bright yellow. With the increase in the concentration it sequentially transitioned to orange-yellow (0.05 mg mL−1), reddish-brown (0.1 mg mL−1), light brown (0.5 mg mL−1), and finally dark brown at the highest concentration (1 mg mL−1), which could be attributed to the strong coordination of the acetyl group in the heroin molecule with the surface of the silver nanoparticles, inducing concentration-dependent directional clustering of the silver nanoparticles. The solution color deepened significantly with the increase of agglomerate size.21
For MET, at concentrations of 0.001–0.05 mg mL−1, the color gradually transitioned from light yellow to grey. As the concentration increases the color changes sequentially to light grey (0.1 mg mL−1), dark grey (0.5 mg mL−1) and off-white (1 mg mL−1). This difference in colour change was attributed to the competition between the amino group in the methamphetamine molecule and the ligand on the surface of the Ag nanoparticles,22 resulting in the aggregation of Ag nanoparticles loaded on the surface of ZIF-8, red-shifting of the SPR absorption peaks of the aggregated Ag nanoparticles, and a gradual change in colour of the solution from light yellow to grey. For ETO, on the other hand, the change in the color gradient of the solutions was not so obvious. As the concentration gradually increased from 0.001 mg mL−1 to 0.05 mg mL−1, the solution colors all showed light yellow, while the solution colors gradually turned into goose-yellow at concentrations of 0.05–1 mg mL−1, and this color change may originate from the weak coordination or competitive adsorption of the imidazole ring or carbonyl group in the etomidate molecule with the silver nanoparticles in ZIF-8/Ag, resulting in slight agglomeration of the Ag particles and a change in the SPR effect. This process is exacerbated by an increasing concentration, but the gradient of color change is not significant due to the weak interaction.
Fig. 4(d)–(f) shows the UV-visible spectrograms of seven concentrations of HER, MET, and ETO, respectively. As can be seen from the figure, the UV spectrograms of HER and ETO are similar, with the intensity of the absorption peaks gradually increasing as the concentration of the solution increases. The UV spectrograms of MET, on the other hand, showed an opposite trend, with the intensity of the absorption peaks gradually decreasing with the increase of the solution concentration, which may be due to the chemical reaction between the high concentration of MET and ZIF/Ag, which led to the decrease or disappearance of the SPR absorption peaks of Ag.
In the detection of these three illicit drugs based on the colorimetric method, the resolution of the naked eye was low, so we introduced SERS for further detection of HER, MET and ETO. Fig. 4(g)–(i) shows the SERS spectra of HER, MET and ETO at 1 mg mL−1, respectively, and it can be seen from the figure that there are obvious differences in the Raman spectra of the different drugs. The characteristic peaks of HER at 624 cm−1 corresponded to the C–CO bending deformation vibration, and those at 1348 cm−1 and 1636 cm−1 corresponded to the C–O stretching vibration and C
C stretching vibration, respectively, and these peaks showed the detection signals of HER, which confirmed the presence of HER.23 The characteristic peaks at 623 cm−1, 1003 cm−1 and 1353 cm−1 were the vibration peaks of MET, among which 623 cm−1 and 1003 cm−1 correspond to the breathing vibration of the benzene ring and 1353 cm−1 corresponds to the twisting vibration of CH2.24 The Raman peaks with stronger signals in the SERS spectrograms of ETO include 615 cm−1, 1002 cm−1 and 1720 cm−1, etc., of which 615 cm−1 and 1002 cm−1 can be attributed to the deformation of the benzene ring, 615 cm−1 and 1002 cm−1 can be attributed to the stretching vibration of benzene ring deformation, and 1720 cm−1 can be attributed to the rocking vibration of O
CO.25 The SERS spectra of these three kinds of illicit drugs all show that ZIF-8/Ag as the SERS substrate has a better signal enhancement effect.
In the actual SERS analysis, the characteristic peak value corresponding to a certain functional group is often chosen as the measurement value. 624 cm−1 is a characteristic of the molecular structure of HER, so the characteristic peak value at 624 cm−1 was selected for the SERS analysis, and similarly, the characteristic peak value at 1353 cm−1 was selected for MET and 1002 cm−1 was selected for ETO. The logarithm of the five concentration values from 0.005 mg mL−1 to 0.5 mg mL−1 of the three drugs was used as the horizontal coordinate, and their corresponding characteristic peaks were used as the vertical coordinate to draw the standard curves, and the results are shown in Fig. 5(d)–(f). The correlation coefficients R2 of the linear curves of the three drugs were 0.99311, 0.98123 and 0.99659, respectively, which showed a good linear relationship; accordingly, the concentration of the substances was quantitatively analyzed by using the SERS peak intensity.
For each sample, 50 μL of treatment solution (0.01 mg mL−1) was taken separately and mixed with 50 μL of ZIF-8/Ag nanocomposite, and the colour change of the mixture was monitored in real time in a well plate over a five-minute period (the recordings were performed every minute, and the colour change was recorded over a five-minute period, over a four-minute period, over a three-minute period, over a two-minute period, and over a one-minute period, respectively, from left to right). As shown in Fig. 7, some of the samples were able to present a better colorimetric effect within five minutes. For the first substance, the color change within five minutes was not obvious, and all were light yellow to the naked eye; the second substance showed more obvious color change, and especially in the fifth minute, there was obvious greyish-white; the third substance was able to show orange-yellow, reddish-brown and other color changes in a shorter time, according to which the three substances could be initially screened, indicating that the target substances might be etomidate, methamphetamine and heroin. The three target substances are etomidate, methamphetamine and heroin.
However, some of the samples existed with low resolution to the naked eye, so after the colourimetric reaction, 20 μL of the reaction solution of each of the three mixed substances was taken onto the silicon wafer and dried at room temperature. SERS detection was carried out and the spectra were collected under a 785 nm laser and 50 μm slit conditions (2 s of exposure, averaged over 3 times for each point), and the SERS spectra of the three substances were obtained (Fig. 7). By comparing with the standard SERS spectra of HER, MET and ETO, it was basically determined that the three seized samples were the above three substances, and the characteristic peaks of the SERS spectra of the three samples were partially shifted due to the interference of possible impurities. The main characteristic peaks of the SERS spectrum of the seized sample of etomidate were at 616 cm−1 and 1003 cm−1, with a displacement deviation of ±1 cm−1 compared with the SERS spectra of the standard substances; the main characteristic peaks of the SERS spectrum of the seized sample of methamphetamine were at 1003 cm−1 and 1350 cm−1, with a displacement deviation of ±3 cm−1; and the main characteristic peaks of the SERS spectrum of the seized sample of heroin were at 625 cm−1 and 1350 cm−1, with a displacement deviation of ±3 cm−1. The main characteristic peaks of SERS for the heroin seized sample were 625 cm−1 and 1350 cm-1 with a displacement deviation of ±2 cm-1. In addition, the SERS characteristic peaks of the three substances were similar, so that ultimately, the accurate identification of the three types of targets could be achieved by the coupling strategy of colourimetric primary screening and SERS dual characteristic peak corroboration.
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