Molecularly Imprinted QCM Sensor Based on Hollow ZIF-67@PDA for Sparfloxacin Detection

Abstract

In this study, we present the design of a molecularly imprinted polymer (MIP) for the detection of the antibiotic sparfloxacin (SPFK), combined with a high-precision quartz crystal microbalance (QCM) sensor. Green-synthesized ZIF-67@PDA-MIP was directly immobilized on the gold electrode surface of the QCM. This configuration takes advantage of the selective recognition capabilities of the MIP and the high-sensitivity response characteristics of the QCM sensor. It overcomes the limitations of traditional SPFK detection methods, offering both accurate detection and rapid responses for practical applications. The MIP-QCM sensor demonstrated enhanced sensitivity and affinity, achieving a detection limit as low as 10.3 ng/mL. Additionally, the selectivity of the sensor for SPFK was superior to that of other non-template molecules. It effectively detected SPFK residues in milk with acceptable accuracy, as indicated by recoveries ranging from 96.16% to 104.64% and a relative standard deviation (RSD) of less than 4.64%. These results suggest that the proposed MIP-QCM sensor provides an accurate, sensitive, rapid, and cost-effective method for detecting SPFK residues in animal products, and this advancement is expected to promote the widespread adoption of high-precision sensors in food safety testing.

1. Introduction

A third-generation quinolone antibiotic, sparfloxacin (SPFX), is widely used in veterinary medicine to treat infections of the skin [1], soft tissues, gastrointestinal tract, respiratory [2], and urinary tract [3]. In recent years, concerns have been raised about SPFX drug residues, and China’s national food standard has established a maximum residue limit (MRL) of 5.0 μg/kg for SPFX in food [4]. Research has indicated that excessive SPFX residues in food can pose significant health risks to humans, potentially leading to allergic reactions in mild cases [5] and damage to the central nervous system in more severe instances [6]. The overuse of antibiotics in lactating dairy cows and inadequate rest periods can result in antibiotic residues in milk, potentially causing adverse effects on human health throughout the food chain. Therefore, the detection of SPFX residues in milk is essential for ensuring food safety.

Current detection methods for SPFX residues include high-performance liquid chromatography (HPLC) [7,8,9], mass spectrometry (MS) [10,11], and fluorescence techniques [12,13,14]. While high-precision detection techniques often require complex, time-consuming sample preparation and costly analytical instruments, in contrast, convenient and time-efficient methods, such as fluorescence colorimetry, are prone to interference from sample turbidity and color, which can compromise the accuracy of the results. Therefore, there is a pressing need for a method that combines the advantages of these different detection techniques while overcoming their respective limitations to improve the practicality of physical detection.

Bio-piezoelectric sensors based on quartz crystal microbalance (QCM) are valuable analytical tools for detecting nanogram-level mass changes by measuring frequency shifts [15,16]. QCM sensors are especially promising for the development of devices to detect pesticide residues in food, owing to their high sensitivity, specificity, rapid real-time detection capabilities, and cost-effectiveness. Moreover, these sensors eliminate the need for complex sample pretreatment procedures, making them ideal for routine food safety monitoring.

With specially crafted cavities intended for the targeted adsorption of template molecules, molecularly imprinted polymers (MIPs) are highly attractive functional materials [17,18]. Compared to conventional biosensor recognition components like enzymes, antibodies, nucleic acids, aptamers, and whole cells, MIPs are more cost-effective, simpler to synthesize, and faster to produce [19,20]. Furthermore, MIPs exhibit exceptional stability across a wide range of recognition environments. Due to their high affinity for template molecules, MIPs have been increasingly utilized as recognition elements on quartz crystal surfaces. When combined with QCM technology, MIPs-QCM sensors leverage the strengths of both materials, showing significant potential in food safety and environmental monitoring applications [21,22,23]. However, conventional methods for synthesizing MIPs typically involve toxic chemicals and large amounts of organic solvents, which pose environmental risks and increase production costs. To address these challenges, green chemistry principles are gaining prominence in the synthesis of MIPs.

In this study, we synthesized a molecularly imprinted polymer–quartz crystal microbalance (MIP-QCM) sensing platform for the highly sensitive and selective detection of SPFK (Scheme 1). Through simple green synthesis methods, ZIF-67 was employed as the carrier, and dopamine hydrochloride served as the polymer monomer, polymerized onto the surface of ZIF-67. The imprinting molecule (SPFX) was incorporated during the polymerization process, resulting in the synthesis of ZIF-67@PDA-MIP after elution. It was spin-coated onto the QCM surface to fabricate a MIP-QCM sensor.

Under optimal conditions, the sensor exhibited an excellent linear correlation with SPFK within a concentration range of 0.03125 to 2.0 μg/mL, with outstanding selectivity for structural analogs and a rapid reaction time. The use of ZIF-67@PDA-MIP for SPFK detection presents a novel, standardized approach for identifying target antibiotics in biological samples with high sensitivity and selectivity.

2. Experimental Part

2.1. Reagents and Materials

HPLC-grade (≥98.0%) analytes of sparfloxacin (SPFX) and its analogs ciprofloxacin, ciprofloxacin (CIP), enrofloxacin (ENRO), flumequine (FPA), and ofloxacin (OFLO)—as well as synthetic, molecularly imprinted polymers of dobutamine hydrochloride, 2-methylimidazole, cobalt nitrate, and methanol with anhydrous ethanol—were obtained from Shanghai McLean Biochemistry and Chemical Science and Technology Company Limited (Shanghai, China). All reagents were commercially available in analytical reagent grade. Deionized water (18.25 MΩ·cm) was used for all experiments.

SPFK individual stock solutions were first made by dissolving 10.0 mg in 100.0 mL of methanol solution to obtain 100.0 μg/mL and stored away from light. The stock solutions were diluted with deionized water to obtain the corresponding standard working solutions. The pure milk tested in this study was purchased from a local supermarket (Chengdu, China).

2.2. Instrumentation

The morphology and structure of the prepared samples were characterized by scanning electron microscopy (SEM, JEOL-2100F, JEOL Ltd., Tokyo, Japan) and transmission electron microscopy (TEM, JSM4800F, JEOL, Tokyo, Japan), while high-resolution TEM (HRTEM) images were obtained by using JSM4800F. Elemental compositions and valence states were analyzed by TEM mapping and X-ray photoelectron spectroscopy (XPS, ESCALAB-250Xi, Shanghai, China), respectively. X-ray diffraction (XRD, DX-2700, Dandong, China) was used to characterize the crystalline structure of the materials. FTIR measurements were performed using attenuated total reflection Fourier transform infrared spectroscopy (IRTracer-100, Shimadzu, Kyoto, Japan). The UV–visible absorption spectra of the supernatant final SPFK were measured by a UV–visible spectrophotometer (UV755B, Shanghai, China). Contact angle measurements were performed by KRÜSS DSA100 (Hamburg, Germany) using the stationary drop method. The surface morphology of the QCM and MIP-QCM chips was observed using an atomic force microscope (AFM, Bruker, Billerica, MA, USA). AT-cut 10 MHz quartz crystals (8 mm in diameter) with gold electrodes (3 mm in diameter) were supplied by Chengdu Tian’ao Electronics Company Limited (Chengdu, China). The sensor parameters were tested by SAUNDERS & ASSOCIATES (250B-2, Bridgehampton, NY, USA).

2.3. Synthesis of ZIF-67@PDA-MIP

2.3.1. Preparation of ZIF-67

Cobalt nitrate hexahydrate (0.291 g, 1 mmol, Micklin) was dissolved in 25 mL of methanol, which was recorded as solution A. At the same time, 2-methylimidazole (0.328 g, 4 mmol, Micklin) was dissolved in another 25 mL of methanol, which was recorded as liquid B. Solution B was poured into the methanol. Liquid B was poured into liquid A, stirred at room temperature for 1 h, left to stand for 24 h, centrifuged at 6000 rpm, washed three times with methanol, and dried at 60 °C to obtain ZIF-67.

2.3.2. Preparation of ZIF-67@PDA-MIP

In total, 100 mg of ZIF-67 was dissolved in 120 mL of Tris-HCl (pH = 8.5) solution with SPFK (200 mg). Another 200 mg of dopamine hydrochloride was dissolved in 80 mL of Tris-HCl (pH = 8.5) solution, and then, the two were mixed and stirred at 500 rpm at room temperature for 24 h. Anhydrous ethanol was used as the eluent of SPFX several times until the UV absorbance of SPFX in the supernatant was reduced to stability; then, after three rounds of washing with ultrapure water, it was dried to obtain ZIF-67@PDA-MIP. The procedure for the synthesis of ZIF-67@PDA-NIP was the same as that described above except that SPFK was not added.

2.4. Adsorption Performance Study of ZIF-67@PDA-MIP

The adsorption method was as follows: ZIF-67@PDA-MIP or ZIF-67@PDA-NIP (2 mg/mL, 0.2 mL) was incubated in different concentrations of SPFK solution (5–70 μg/mL, 1.8 mL). After two hours of incubation, the supernatant was separated from ZIF-67@PDA-MIP or ZIF-67@PDA-NIP by centrifugation (6000 rpm), and the concentration of SPFK in the supernatant was determined by a UV spectrophotometer. The mass of SPFX adsorbed on MIP or NIP was calculated by the following equation:

$Q_e=(C_0-C_e)V/m$

where C₀ (mg/mL) and C_e (mg/mL) are the initial and final concentrations of SPFK, respectively; V (mL) is the volume of the solution; and m (g) is the mass of the polymer.

The recognition performance of MIP for specific hexaconazole was evaluated using the imprinting factor (IF), which was denoted as IF = Q_MIP/Q_NIP, where Q_MIP and Q_NIP are the adsorption amounts of the ZIF-67@PDA-MIP and ZIF-67@PDA-NIP templates, respectively.

2.5. Preparation of MIP-QCM Sensor

The quartz crystal gold electrodes were cleaned in ethanol by ultrasonication before modification and then immersed in a new “water tigerfish” solution (30% H₂O₂/concentrated H₂SO₄ = 1:3, V/V) for 5 min. After thorough cleaning, the electrodes were dried with nitrogen. We accurately weighed 10 mg of ZIF-67@PDA-MIP dissolved in ultrapure water, and sonication and vortex shaking were used to evenly disseminate the mixture until a homogenous suspension (1 mg/mL) was achieved, and the gold electrode layer was evenly covered with the mixture (3.0 µL). The redesigned electrode layer was mounted with a quartz crystal microbalance before use and kept dry at room temperature.

Optimization of Detection Conditions for MIP-QCM Sensors

To achieve the maximum sensitivity of SPFX molecularly imprinted QCM electrodes in practical detection, the effects of coating volumes of 0.5, 1, 1.5, 2, 3, 4, and 5 µL on the response frequency of the QCM sensors were explored to determine the optimal coating volume of the MIP-QCM.

2.6. QCM Sensor Measurements

Appropriate amounts of SPFX standard solutions of different concentrations (all lower than those required for adsorption saturation) were added dropwise to the surface of the MIP-QCM and equilibrated at room temperature for ten minutes. Unbound SPFX was washed away with deionized water, the chip was dried, the frequency change was measured, and a frequency–concentration linear curve was plotted. Selective analysis was performed through the dropwise addition of equal amounts of CIP, ENRO, FPA, and OFLO standard solutions of the same concentrations on the surface of the MIP-QCM, with the same experimental steps as above.

2.7. Preparation of Real Samples

Milk samples were processed as described in [24]. Briefly, 5 mL of milk was taken and 45 mL of acetate buffer (0.1 mol/L, pH = 5.5) was added. Then, SPFK standard solution was added to obtain final SPFK concentrations of 0.0625 and 0.25 μg/mL. Spiked samples were rotated and shaken for 1 min and stored at 4 °C.

3. Results and Discussion

3.1. Morphological and Structural Characterization of ZIF-67@PDA-MIP

Figure 1A shows SEM images of ZIF-67 crystals, which exhibit a rhombic dodecahedral shape. Dopamine was added to a suspension of ZIF-67 in Tris-HCl solution (pH 8.5, including SPFX) to start a one-step transformation reaction, which was allowed to react for 24 h at room temperature. The ethanol elution of SPFX yielded ZIF-67@PDA-MIP.

Figure 1B,C display SEM images of ZIF-67@PDA-NIP and ZIF-67@PDA-MIP, respectively. There was no significant change in particle size after the transformation; however, the smooth surface became rougher, the edges became less defined, and the morphology transitioned from a dodecahedral to a spherical-like structure. The chemical etching process associated with the formation of PDA also resulted in a hollow interior [25,26]. The TEM images shown in Figure 1D,E further illustrate the hollow structure of the prepared ZIF-67@PDA-MIP, with distinct edges indicating the formation of the PDA layer.

Figure 1F confirms the presence of elements Co, C, O, and N in the hollow structural shell, as verified by EDS. Additionally, the line-scan results depicted in Figure 1G show the distribution curves illustrating variations in the content of these elements.

FT-IR measurements were conducted to validate the molecular imprinting process. The FT-IR spectra of SPFK, ZIF-67@PDA-MIP, and ZIF-67@PDA-MIP adsorbed with SPFK are shown in Figure 2A. Distinctive SPFK absorption bands appear at 1639 cm⁻¹ and 1710 cm⁻¹, corresponding to the ν(CO) pyridine and ν(CO) carboxylate stretching modes, respectively. A peak near 1085 cm⁻¹ can be attributed to the stretching vibration of the C-F group [27]. Additional signals include aromatic N-H stretching at 3460 cm⁻¹, O-H bending at 1439 cm⁻¹, and C-N stretching at 1341 cm⁻¹ [28].

For ZIF-67@PDA-MIP, the characteristic peaks of SPFK were significantly weakened or even disappeared, indicating the successful elution of SPFK. Upon the re-adsorption of SPFK onto ZIF-67@PDA-MIP, characteristic peaks of SPFK reappeared, confirming that the ZIF-67@PDA-MIP successfully generated the imprinted cavity and was able to adsorb the template molecule SPFK once again.

The synthesized ZIF-67@PDA-MIP was characterized using various techniques, including XRD, FT-IR, and Raman spectroscopy, with typical results illustrated in Figure 2. XRD Analysis (Figure 2B). The XRD results indicate strong diffraction peaks for ZIF-67, suggesting good crystallinity [29]. However, after the PDA modification, the intensity of these peaks decreased or even disappeared, likely due to an etching effect from the PDA treatment.

FT-IR spectroscopy was carried out as Figure 2C illustrates. ZIF-67’s FT-IR spectra show distinctive absorption bands between 993 and 1419 cm⁻¹, which can be ascribed to the imidazole ring’s bending and stretching vibrations. The stretching vibration of the Co-C bond is represented as a peak at 424 cm⁻¹. The modest absorption at 2930 cm⁻¹ represents the C-H stretching vibration in 2-methylimidazole (2-MI), whereas the band at 1570 cm⁻¹ is linked to the C=N stretching vibration of 2-MI as a ligand. Compared with ZIF-67, three additional peaks appeared in the spectra of ZIF-67@PDA-NIP and ZIF-67@PDA-NIP at 1610 cm⁻¹, 1490 cm⁻¹, and 1050 cm⁻¹, which were due to the C-C stretching, C-N vibration, and N-H vibration of PDA, respectively; this confirms the presence of a PDA layer on ZIF-67 [25,30].

The Raman results provide insight into the degree of defects in the material (Figure 2D). The ZIF-67 spectrum shows several low-intensity peaks in the lower Raman shift region, attributable to Co ions. Peaks at 426 and 677 cm⁻¹ correspond to Co-N bonds and 2-methylimidazole ligands, respectively [31]. For ZIF-67@PDA-MIP, a peak at 1590 cm⁻¹ indicates the presence of sp²-hybridized carbon structures (G-band), while a peak at 1365 cm⁻¹ signifies defects (D-band) [32]. An ID/IG ratio of 0.87 suggests that the PDA treatment disrupted the original ZIF-67 structure, introducing a significant number of surface defects.

The elemental composition and chemical states of ZIF-67@PDA-MIP were analyzed using X-ray photoelectron spectroscopy (XPS), with the relevant spectra illustrated in Figure 3. The XPS total spectrum of ZIF-67@PDA-MIP confirmed the presence of the elements Co, O, N, and C (Figure 3A). For Co 2p, the Co 2p spectrum of ZIF-67@PDA-MIP consists of two spin–orbit double peaks corresponding to the Co 2p_1/2 and Co 2p_3/2 regions (Figure 3B). The Co 2p spectral peaks were deconvoluted into three different components, specifically denoted as Co³⁺, Co²⁺, and satellite peaks [33]. The peaks at 785.4 and 801.8 corresponded to Co²⁺, and the peaks at 781.3 and 796.9 eV can be attributed to Co³⁺, which indicates that part of the Co²⁺ binds to the PDA, and the rest of the Co²⁺ reacts with oxygen in the air to produce cobalt oxide. Given the O 1s spectrum, the two main peaks at 532.3 and 531.4 eV can be attributed to O=C and O-C, respectively (Figure 3C) [34]. In the N 1s spectrum, the three typical components located at 398.5, 399.85, and 401.35 eV corresponded to pyridine- (=N-), pyrrole- (-NH-), and graphite (-NH₂)-type N atoms, respectively (Figure 3D) [35], and the presence of the amino group in the ZIF-67@PDA-MIP revealed a successful modification of the PDA, as ZIF-67 contained only pyridine- and pyrrole-type N atoms. Figure 3E shows a C 1s spectrum with three peaks at 284.8, 285.5, and 287.6 eV, corresponding to C-C, C-O, and C=O, respectively, again indicating the generation of polydopamine on the ZIF-67 surface [36].

3.2. Adsorption Properties of ZIF-67@PDA-MIP

SPFX was selected as the target molecule to examine ZIF-67@PDA-MIP’s adsorption characteristics. Anhydrous ethanol served as the eluent, and the elution degree was quantified by measuring the decrease in UV absorbance at 298 nm (Figure 4A). A calibration curve was constructed using varying concentrations of SPFX standard solution (0.5–70 μg/mL), yielding a linear regression equation of y = 0.027x + 0.088 with a high correlation coefficient R² = 0.997 (Figure 4B). The isothermal adsorption experiments, illustrated in Figure 4C, demonstrated that the adsorption capacity of both ZIF-67@PDA-MIP and ZIF-67@PDA-NIP increased with rising SPFX concentrations. Initially, the equilibrium adsorption capacity grew slowly, with MIP consistently exhibiting a higher adsorption capacity for SPFX compared to NIPs until saturation was reached. When the adsorption process starts, the equilibrium capacity increases gradually, with the adsorption capacity of MIP for SPFX consistently outperforming that of NIP until saturation is achieved. At lower concentrations, ZIF-67@PDA-MIP demonstrated an impressive equilibrium adsorption capacity of 54.15 mg/g, significantly exceeding that of ZIF-67@PDA-NIP, which recorded 25.16 mg/g.

This enhanced adsorption capacity is likely due to a superior alignment between the recognition sites on the surface of the MIP and the SPFX template molecules, allowing for more effective binding and absorption. Furthermore, the calculated imprint factor for ZIF-67@PDA-MIP was 2.15, indicating that the recognition sites on its surface are particularly adept at selectively re-binding the target molecule SPFX, thereby affirming the efficacy of the MIP design in capturing the intended analyte. These results suggest that ZIF-67@PDA-MIP could be highly effective for applications in selective adsorption and separation processes.

3.3. Exploration of MIP-QCM Performance

After the preparation of SPFK-imprinted and non-imprinted QCM sensors, they were characterized using contact angle (CA) measurements and atomic force microscopy (AFM), as illustrated in Figure 5A–C. The CA value for the unmodified QCM surface was measured at 88.9°. For the modified surfaces, the CA values were 79.3° for the NIP and 65.2° for the MIP. The observed changes in CA values during the imprinting process can be attributed to the hydrophilic nature of the polydopamine on the ZIF-67@PDA-MIP surface, along with an increase in surface roughness [37].

The AFM images in dynamic mode, shown in Figure 5D–F, reveal the morphology of the QCM sensor surfaces. The average surface roughness was determined to be 8.29 nm for the MIP-QCM and 17.6 nm for the NIP-QCM. These roughness values support the conclusion that successful film formation occurred on the QCM chip surface. Additionally, the thicknesses of the polymer films were found to be 30.11 nm for the MIP and 34.18 nm for the NIP, indicating the effective attachment of the polymer films to the gold surface of each QCM sensor. These characterizations confirm the successful modification of the QCM sensors, enhancing their potential for selective detection applications.

In this study, the spin-coating method was employed to stabilize and immobilize ZIF-67@PDA-MIP on the surface of QCM electrodes. The number and thickness of imprinted binding sites on the modified membrane are directly influenced by the amount of MIP, which also has an impact on the sensitivity and reaction time of the sensor [38]. As illustrated in Figure 6A, the sensor response frequency initially increased with the coating amounts of MIP (0.5, 1, 1.5, 2, 3, 4, and 5 µg), peaking at 1.5 mg. Beyond this point, additional MIP loading led to a decrease in response frequency, indicating that excessive MIP can hinder the selective adsorption of analytes at the binding sites, thus weakening the sensor’s response.

How the sensor reacts to different SPFK standard solution concentrations (0.03125–2 μg/mL) was also examined at the optimal MIP concentration of 1.5 mg, with three replicates for each measurement, as shown in Figure 6B. The results demonstrate a clear enhancement in sensor response frequency with increasing SPFK concentration. The derived regression equation for the MIP-modified sensor within this concentration range was Y = −124.1X − 69.57 (with an R² value of 0.998), indicating strong predictive capability. The limit of detection (LOD) was calculated to be 10.3 ng/mL using the formula LOD = 3.3S/δ, where δ represents the residual standard deviation of the blank sample, and S is the slope of the regression line.

Additionally, the frequency variation observed in the MIP-modified sensor was significantly greater than that of the NIP-QCM, highlighting the enhanced specificity and sensitivity provided by the MIP modification. This study underscores the importance of optimizing MIP loading to achieve the best sensor performance.

CIP, ENRO, FPA, and OFLO were selected as analogs of SPFK to evaluate the selectivity of the sensors constructed with modified QCM electrodes. As shown in Figure 6C, the QCM sensor exhibited response frequencies to these quinolone antibiotics in the following order: SPFK > CIP > FPA > ENRO > OFLO. This demonstrates that the sensor has the highest selective recognition for SPFK, indicated by the largest response frequency among the tested analytes.

The reproducibility and stability of the MIP-QCM were determined (Figure 7). Regarding repeatability, after five cycles of repeated elution, we observed a gradual decrease in the frequency of the membrane. Specifically, the frequency difference between the fifth elution and the initial frequency exceeded 50 Hz. This decline may be due to small parts of the membrane detaching during the repeated ultrasonication process. As for stability, the sensor demonstrated good performance, with stability remaining above 95% after one week.

To further emphasize the advantages of the proposed sensing method, the performance of the constructed sensors was compared to previously reported methods for SPFK detection (Table 1). Notably, the ZIF-67@PDA-MIP used in this study stands out as a low-cost and easily prepared molecularly imprinted material for sensor modification. The QCM method developed here not only exhibits a broad linear detection range but also boasts a low detection limit. This capability is particularly beneficial for detecting trace amounts of SPFK in various matrices, including food.

Overall, the MIP-QCM sensing method presented in this study proves to be practical and effective, with the ZIF-67@PDA-MIP offering significant advantages as a sensitive material for molecularly imprinted sensors.

3.4. Real Sample Analysis

To assess the performance of the constructed sensors, a spiked recovery test was conducted using milk samples purchased from local supermarkets. After a simple pretreatment, SPFK was spiked into the samples at concentrations of 0.0625 and 0.25 μg/mL. Each concentration was tested three times, as detailed in Table 2.

The recovery rates for the two spiked levels ranged from 96.16% to 104.64%, with a relative standard deviation (RSD) of ≤4.64%. These results indicate that the method is both accurate and straightforward, requiring minimal pretreatment and reducing overall costs. Importantly, the substrate had no significant effect on the detection of SPFK, demonstrating the reliability of the sensor in various sample matrices.

Overall, the constructed sensor is effective for detecting SPFK in milk samples, confirming its feasibility for practical applications after simple pre-processing. This makes it a promising tool for monitoring antibiotic residues in food products.

4. Conclusions

In this study, we developed a ZIF-67-derived MIP-QCM sensor specifically designed for the rapid detection of SPFK in milk. A characterization of the nanocomposites, synthesized using environmentally friendly methods, was conducted using various microscopy and spectroscopy techniques, confirming their structure and composition. The fabricated MIP-QCM sensor demonstrated impressive sensitivity and selectivity, exhibiting a linear detection range of 0.03125 to 2 μg/mL and a low detection limit of 10.3 ng/mL. This high performance indicates the sensor’s ability to detect trace amounts of SPFK effectively. Moreover, the MIP-QCM chip is portable and can be stored for extended periods without requiring expensive instrumentation, making it highly practical for field applications. This study opens new avenues for the trace detection of SPFK in food products, enhancing food safety and monitoring practices.

Author Contributions

S.L.: conceptualization; funding acquisition; methodology; writing—review and editing. L.W.: conceptualization, data curation, investigation, writing—original draft. C.C.: formal analysis; methodology; software. L.X.: software; supervision. H.W.: resources; supervision. P.Y.: resources; software; supervision. M.S.: formal analysis; methodology; supervision. F.T.: funding acquisition; resources; supervision. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

The data will be made available upon request.

Conflicts of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Figures, Scheme and Tables

Scheme 1. Synthesis of ZIF-67@PDA-MIP for SPFK detection and construction of MIP-QCM sensor.

Figure 1. Morphological characterization of ZIF-67@PDA-MIP. SEM image of (A) ZIF-67, (B) ZIF-67@PDA-NIP and (C) ZIF-67@PDA-MIP; (D,E) TEM image of ZIF-67@PDA-MIP; (F) EDS elemental map of ZIF-67@PDA-MIP; (G) ZIF-67@PDA-MIP distribution curves of different elemental content variations in the same MIP region.

Figure 2. (A) FT-IR spectra of ZIF-67@PDA-MIP before and after SPFK adsorption; (B) XRD patterns, (C) FTIR spectra and (D) Raman spectra (The characteristic Raman peaks of ZIF-67 are marked with *) of ZIF-67, ZIF-67@PDA-NIP and ZIF-67@PDA-MIP.

Figure 3. XPS profiles of ZIF-67, ZIF-67@PDA-NIP, and ZIF-67@PDA-MIP. (A) XPS total spectrum, (B) Co 2p, (C) C 1 s, (D) N 1 s and (E) O 1 s spectras of ZIF-67@PDA-MIP.

Figure 4. UV-assessed adsorption effects. (A) Elution effect of MIP. (B) Linear curve of SPFK absorbance with concentration. (C) Static adsorption isotherms of different concentrations of SPFK on MIP and NIP.

Figure 5. MIP-QCM chip characterization contact angle on the chip surface of (A) a bare chip, (B) NIP and (C) MIP. AFM 3D view of the chip surface of (D) a bare chip, (E) NIP and (F) MIP.

Figure 6. Determination of MIP-QCM. (A) Frequency variation in the sensor with different MIP coating amounts. (B) Concentration calibration curve of MIP-QCM. (C) Selectivity determination for MIP-QCM.

Figure 7. (A) Reproducibility and (B) stability of MIP-QCM.

Table 1

Comparison of different analytical methods for SPFK.

Analytical Methods	Range	LOD	Reference
RP-HPLC	15–105 μg/mL	450 ng/mL	[39]
HPTLC	0.1−0.6 μg/spot	13 ng/spot	[40]
Fluorescence	0.28–40 μg/mL	83.7 ng/mL	[41]
MIP-Fluorescence	0.05–2 μg/mL	12 ng/mL	[42]
Fluorescence	0.5–1000 μg/mL	1000 ng/mL	[43]
DES-DLLME-qNMR	0.4–60 μg/mL	100 ng/mL	[44]
Fluorescence	0.2~2.2 μg/mL	70 ng/mL	[45]
TLC-SERS	0.0125–0.05 μg/mL	19 ng/mL	[4]
MIP-QCM	0.03125~2 μg/mL	10.3 ng/mL	This work

Table 2

The recovery of real samples detected by ZIF-67@PDA-MIP (n = 3).

Sample	Detected by This Method
	Add (μg/mL)		Frequency Variation (Hz)	Found (μg/mL)	Recovery (%)	RSD (%)
Milk 1	1	0.00		Not Found
	2	0.0625	77.69	0.0654	104.64	4.64
	3	0.25	101.38	0.256	102.40	2.4
Milk 2	1	0.00		Not Found
	2	0.0625	77.03	0.0601	96.16	3.84
	3	0.25	100.93	0.253	101.20	1.20

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