Nitrofuran is a typical broad-spectrum antibiotic. Its derivatives and nitrofuran compounds are widely used in clinical practice and veterinary medicine and can be employed to preserve animal feed, prevent and treat gastrointestinal infections caused by bacteria, and accelerate animal growth. However, studies have proven that nitrofuran and its metabolites have carcinogenic and teratogenic side effects on humans and that diseases such as hemolytic anemia and acute liver necrosis can also occur if excess nitrofuran antibiotics are consumed. This has gradually caused concern. Therefore, high-sensitivity monitoring of nitrofuran is important for safeguarding human health and life safety. Traditional methods such as chromatography, enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-mass spectrometry (LC-MS) have the disadvantages of a long pre-treatment and analysis period, cumbersome processing, massive sample usage, and a high false-positive rate of test results. Therefore, it is necessary to find a rapid, accurate, and stable assay for monitoring the use of nitrofuran drugs. As biological samples are often present in a diluted state, sensitive detection of biomolecules without any binding site markers or aids remains challenging. Metamaterials have unique optical properties and exhibit unique characteristics, such as local electric field enhancement, which can be tuned by the geometric design of metamaterials. The electric field enhancement in metamaterials can improve the interaction between the sample and terahertz (THz) waves. Thus, the use of THz metamaterials as a sensing platform can overcome the low sensitivity of biological samples in the THz range and enable biomolecular detection in a label-free manner. We hope that the use of metamaterials will enable the non-destructive and rapid detection of nitrofuran drugs.

THz waves are parts of electromagnetic waves between far infrared and microwave, which have good safety and fingerprinting properties for substance identification without damaging effects on substances. The basic principle of THz time-domain spectroscopy is to use femtosecond pulses to generate and detect time-resolved THz electric fields and to obtain spectral information of the measured item through the Fourier transform. Since the vibration and rotation energy levels of macromolecules are mostly in the THz region, and macromolecules, especially biological and chemical macromolecules, are groups of substances with physical properties, the structure and physical properties of substances can thus be analyzed and identified through characteristic THz frequencies. Meta-surfaces are two-dimensional artificial sub-wavelength periodic structures that can better respond to electromagnetic waves compared to natural materials. The electromagnetic waves are modulated by the change in the shape and size of the structure. A change in the refractive index of a sample attached to the surface of a meta-surface sensor can alter the local field of the meta-surface, which is reflected by the change in the resonance peak of the spectrum. In this paper, a symmetrical open-ring meta-surface structure is designed, which has two layers. The open-ring surface structure is constructed from metallic aluminum (Al), and the substrate structure is constructed from polyimide (PI). PI is a flexible material that has the advantages of a small dielectric constant and stable properties and is non-damaging to biological materials. Simulations of the meta-surface are based on the simulation software CST Studio Suite with a full-vector finite element method (FEM). The structure has a refractive index sensitivity of 196 GHz/RIU and can be applied for high-sensitivity sensing detection. Experiments are performed with different mass concentration gradients of furazolidone and furantoin solutions. 60 μL of different mass concentrations of analytes are added dropwise to the meta-surface structure by a pipette, and then it is heated to 50 ℃ and left to dry. THz pulses are incident vertically on the furan-covered meta-surface for spectral acquisition.

The meta-surface structure designed in this paper is simple and has a low processing cost, and its detection is more intuitive and faster and requires fewer samples than conventional methods. The refractive index sensitivity of 196 GHz/RIU is achieved when the refractive index n varies from 1.0 to 1.8, which allows the structure to be used as a high-sensitivity refractive index sensor (Fig. 7). To demonstrate the enhanced detection capability of the meta-surface structure for nitrofuran drugs, we measure THz spectra before and after the dropwise addition of the furazolidone solution to the polyimide substrate. No significant change in the transmission spectrum is observed. In contrast, the meta-surface structure shows a significant red shift in the position of the transmission peak after the dropwise addition of the furazolidone solution (Fig. 8). In the measurement of the THz transmission spectra of furazolidone and furantoin in the mass concentration range of 10-1000 mg/dL, there is a regular red shift at the resonant frequency of the sensor with the increasing concentration and a significant frequency shift. The experimental results indicate that the meta-surface structure can effectively enhance the interaction between furazolidone and THz waves with high sensitivity. The results of several experiments demonstrate that the limited detection mass concentration of 10 mg/dL for both furazolidone and furantoin is achieved (Figs. 10 and 13). This meta-surface is expected to be used for highly sensitive sensing detection.

In this paper, the resonance characteristics and sensing performance of a THz meta-surface sensor based on a symmetrical open ring are investigated. Theoretical simulations show that its refractive index sensitivity reaches 196 GHz/RIU and can be applied to high-sensitivity sensing detection. The results indicate that the sensor can detect two nitrofuran drugs (furazolidone and furantoin) at a minimum mass concentration of 10 mg/dL. This sensing method is mainly based on the difference in dielectric properties of the analytes to be measured, and thus, the meta-surface structure can be applied to the detection of other antibiotics or biochemical samples. This provides a good theoretical and experimental basis for the future development of high-sensitivity sensors.