A method for detecting terahertz fingerprints of biochemical molecules

Abstract

This invention discloses a method for detecting terahertz fingerprints of biochemical molecules, belonging to the fields of artificial surface plasmonics and terahertz spectroscopy applications. This method couples artificial surface plasmons generated by a metal structure with Rayleigh anomalous diffraction generated by a periodic array to form a surface lattice resonance mode, enabling detection of terahertz fingerprints of biochemical molecules. The process required by this method is simple and versatile, and is compatible with Si-based CMOS processes.

Description

Technical Field

[0001] The present invention relates to the technical field of artificial surface plasmonics and terahertz spectroscopy applications, and in particular to a method for detecting terahertz fingerprint spectra of biochemical molecules. Background Art

[0002] Biosafety and human health are key issues in today's society. Rapid, sensitive, and accurate detection of biochemical substances is a necessary means for biosafety prevention and human health monitoring. Biochemical substance detection based on terahertz (THz) waves is a relatively new spectroscopic sensing technology with many unique advantages: (1) Revealing the low-frequency collective vibration fingerprint pattern of molecules, that is, it can reflect the skeleton rotation and vibration mode of biological macromolecules such as nucleic acids, proteins, and sugars; the energy levels of these biochemical molecules fall exactly within the THz spectrum range. Through THz wave technology, the THz spectral fingerprint characteristics of different biochemical substances can be obtained to achieve accurate identification and detection. (2) Rapid detection. THz-TDS technology can obtain time-domain spectral signals with good resolution in just a few seconds, thereby accurately obtaining the absorption and refraction parameters of the biochemical substance to be tested. (3) Non-ionizing detection. The photon energy of THz waves is extremely low, and it can detect living cells in a non-ionizing manner. Compared with X-ray, fluorescence, and radionuclide methods, it can more comprehensively maintain the biological activity of the living cells to be tested. Furthermore, compared to existing infrared and Raman spectroscopy detection methods, THz spectroscopy still offers the advantages of being contactless and label-free. Therefore, THz spectroscopy sensing technology holds broad application prospects. However, due to the weak interaction between free-space THz waves and biochemical substances, the resulting THz energy spectrum has a low response to the biochemical substances being detected. Consequently, conventional THz biochemical detection techniques suffer from low sensitivity, require large sample volumes, are unsuitable for low-concentration detection, and are particularly disadvantageous for detecting expensive samples, failing to meet the demand for highly sensitive biochemical detection.

[0003] Metamaterials are artificial composite electromagnetic materials with unique physical properties not found in natural materials, such as negative refractive index and electromagnetically induced transparency. By designing and combining specific metallic unit structures, metasurfaces with unique optical properties can be created. To address the weak interaction between THz waves and biochemical substances, researchers are primarily using metasurface sensors to enhance THz detection sensitivity. By rationally designing the metasurface structure, the metasurface exhibits high sensitivity to the refractive index changes caused by the addition of a sample, enabling highly sensitive detection of biochemical substances.

[0004] Currently, various THz metasurfaces are designed based on principles such as Fano resonance and electromagnetically induced transparency to improve sensor performance. However, these metasurfaces have complex unit structures, high design and manufacturing costs, and long development cycles. Furthermore, their single resonance mode and uncontrollable peaks significantly limit the application of THz metasurface sensors. On the other hand, the surface lattice resonance peak is modulated by the metasurface period. By varying the period, the position of the resonance peak can be manipulated to couple the THz "fingerprint" spectrum of the biochemical being measured, improving the sensor's detection accuracy. Summary of the Invention

[0005] In response to the shortcomings of the existing technology, the present invention provides a method for detecting the terahertz fingerprint spectrum of biochemical molecules. By coupling the artificial surface plasmons generated by the metal structure and the Rayleigh anomalous diffraction generated by the periodic array, a surface lattice resonance mode is formed to realize the detection of the terahertz fingerprint spectrum of biochemical molecules.

[0006] The technical solutions provided by the present invention are as follows:

[0007] A method for detecting terahertz fingerprints of biochemical molecules, characterized in that:

[0008] 1) preparing a terahertz metasurface sensor having a three-layer structure, wherein the bottom layer is a metal layer, the middle layer is a dielectric layer, and the top layer is a planar array of periodically arranged metal structures, wherein the periodic dimensions of the metal structures in the x-direction and the y-direction are the same;

[0009] 2) Utilizing artificial surface plasmons and the metal structure in the top layer to generate Rayleigh anomalous diffraction coupling, the terahertz metasurface sensor forms a surface lattice resonance mode;

[0010] 3) According to formula (1), calculate the surface lattice resonance peak f of the terahertz metasurface sensor SLRs :

[0011]

[0012] When θ=0°, the formula can be simplified to:

[0013]

[0014] where c is the speed of light in a vacuum, n eff is the effective refractive index of the interface between the middle dielectric layer and the top metal layer, θ is the angle between the incident terahertz wave vector k and the z axis, m and n are integers of the diffraction order in the x and y directions, and P is the periodic size of the metal structure in the x and y directions;

[0015] 4) Using the position of the surface lattice resonance peak of the terahertz metasurface sensor obtained in step 3) to couple the terahertz fingerprint spectra of different biochemical molecules, thereby realizing the detection of the terahertz fingerprint spectra of the biochemical molecules.

[0016] The bottom layer is made of gold, silver or copper, and has a thickness of H1, where H1 is ≥ 0.04 μm.

[0017] The intermediate layer is made of silicon dioxide, polytetrafluoroethylene or polyimide, and has a thickness of H2, 0.8 μm≤H2≤1.50 μm.

[0018] The top metal structure is made of gold, silver or copper, and has a thickness of H3, where H3 is ≥ 2.0 μm.

[0019] The metal structure is a rectangular, open ring, cross or double rectangular structure.

[0020] The present invention has at least the following technical advantages:

[0021] (1) Easy preparation and simple process. The sensor designed in the present invention has a simple top metal structure and is easy to process. The required process flow is simple and universal, compatible with Si-based CMOS technology, with a short preparation cycle, and is easy to mass produce.

[0022] (2) High quality factor and sensitivity. Surface lattice resonance can significantly suppress radiation loss, causing the resonance peak to narrow sharply. In addition, due to the presence of the metal reflective layer, the local electromagnetic field intensity of the top structure is increased, making the sensor very sensitive to small refractive index changes in the outside world.

[0023] (3) Wide range of applications. The present invention can detect most biochemical molecules by changing the period to adjust the position of the resonance peak to couple the terahertz "fingerprint spectrum" of the biochemical substance to be tested. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Schematic diagram of the terahertz metasurface sensor structure and the generated surface lattice resonance mode of the present invention;

[0025] Figure 2 This is an image of a rectangular structure terahertz metasurface sensor under an optical microscope;

[0026] Figure 3 The simulated reflection spectra of the rectangular structure terahertz metasurface sensor at incident angles θ = 0° (dashed line) and θ = 30° (solid line);

[0027] Figure 4 Surface current distribution (a) 0.91 THz; (c) 3.94 THz and surface electric field distribution (b) 0.91 THz; (d) 3.94 THz of rectangular structure terahertz metasurface sensor (incident angle θ = 30°) at the resonant frequency point.

[0028] Figure 5 Simulated (solid line) and measured (dashed line) reflection spectra of the rectangular structure terahertz metasurface sensor (incident angle θ = 30°);

[0029] Figure 6 Terahertz fingerprint spectra of biochemical substances (a) racecadotril; (b) clorazepate;

[0030] Figure 7 To adjust the lattice period of the rectangular structure terahertz metasurface sensor (incident angle θ = 30°) to couple the reflection spectrum of the terahertz fingerprint spectrum of biochemical substances. DETAILED DESCRIPTION

[0031] The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of use of the present invention. After reading the present invention, those skilled in the art will be able to modify various equivalent forms of the present invention within the scope of the appended claims.

[0032] The structure and principle diagram of the terahertz metasurface sensor of the present invention are shown in the figure below: Figure 1 As shown. It consists of three layers of materials from bottom to top. The bottom layer is a thick metal layer, the middle layer is a dielectric layer, and the top layer is a planar array of periodically arranged metal structures. Each metal structure in the array is used to control light. The size of the metal structure in the x direction is P X , the size in the y direction is P Y ;P X =P Y =P, the thickness of the bottom metal layer is H1; the thickness of the intermediate dielectric layer is H2; and the thickness of the top metal structure is H3. The entire sensor is fabricated on a high-resistance silicon substrate. The fabrication steps are as follows:

[0033] (1) Preparation of bottom metal: To avoid the transmission of terahertz waves, one of the three materials, gold, silver, and copper, can be selected. The thickness of the metal substrate H1 is required to be ≥ 0.04 μm.

[0034] (2) Preparation of the intermediate dielectric layer: In order to reduce the dielectric loss of the sensor, a material with a low relative dielectric constant and a thin thickness, such as silicon dioxide, polytetrafluoroethylene or polyimide, can be used. The thickness of the dielectric layer should be 0.8 μm ≤ H2 ≤ 1.50 μm.

[0035] (3) Imaging: The designed metal structure array is obtained through the layout design steps of spinning, pre-baking, UV lithography, development, fixing, and post-baking. The shape of the metal structure can be designed arbitrarily. In order to reduce the difficulty of processing, it can be designed into a rectangular, open ring, cross, double rectangular, etc.

[0036] (4) Graphic transfer: Through electroplating and stripping, a planar array with a periodic arrangement of the top metal structure is finally obtained. The metal structure can be made of one of the three materials: gold, silver, and copper (which can be different from the bottom metal material). The thickness of the top metal array is required to be H3 ≥ 2.0 μm.

[0037] Taking the rectangular metal structure as an example, P X =150μm, P Y =150μm, H1=0.4μm, H1=1.0μm, H3=2.4μm. The bottom and top metals are both made of gold, with a conductivity of 4.561×10 7 S / m, the middle dielectric layer uses silicon dioxide, and the dielectric constant is 3.75+j0.004. The optical microscope photo of the processed sample is as follows Figure 2 shown.

[0038] Figure 3 The simulated reflection spectra of the rectangular structure terahertz metasurface sensor under different incident angles of terahertz waves are the surface lattice resonance. The first group is the peak J at around 0.91 THz, which is caused by the excitation of artificial surface plasmons by the metal structure unit and is not affected by the change of the incident angle. Therefore, its electric field distribution is mainly confined to the area around the rectangular structure, and the surface current presents a dipole resonance state. The second group is the peaks K and L located near 3.44 THz and 3.94 THz respectively. These two peaks are caused by the resonance of the artificial surface plasmon and the Rayleigh anomaly coupling. The surface electric field is distributed on the surface of the metal structure, forming a grating-like standing wave, and the electric field intensity is significantly higher than that of the artificial surface plasmon, as shown in Figure 2. Figure 4 As shown in the color bars in . The surface current forms two vortices that capture the incident energy near the surface of the unit structure, exciting the resonant mode of the adjacent unit structure instead of decaying into free space. Therefore, the surface lattice resonance suppresses radiation loss, which is reflected in the reflection spectrum with a peak resonance frequency of 3.94 THz and a linewidth of 38 GHz, and a Q value of approximately 104.2. This demonstrates that the terahertz metasurface sensor forms a surface lattice resonance mode. The metal structure in the terahertz metasurface sensor of the present invention can be a double rectangular structure, a cross structure, or an open ring structure. Experiments have shown that the simulated and tested reflection spectra of the surface lattice resonance of the above-mentioned terahertz metasurface sensor under terahertz waves have the same properties as those of the rectangular structure terahertz metasurface sensor, that is, any structure can generate surface lattice resonance by optimizing parameters.

[0039] When P=150μm, θ=30°, m=1, n=0, n eff =0.334, the frequency of the surface lattice resonance of the metasurface structure with a periodic array can be calculated as:

[0040]

[0041] like Figure 5 As shown in the figure, the calculated (3.99 THz) surface lattice resonance frequencies are not much different from those of the simulation (3.94 THz) and the measured (4.13 THz), which confirms the feasibility of the surface lattice resonance theory in the terahertz band.

[0042] like Figure 6 、 Figure 7 As shown, the present invention utilizes the lattice period to adjust the position of the surface lattice resonance peak to couple the terahertz fingerprint spectra of different biochemical molecules (such as the drugs racecadotril and loratadine), thereby achieving accurate detection of biochemical substances.

[0043] In summary, the proposed terahertz metasurface sensor, based on a three-layer structure consisting of metal, dielectric layer, and metal, with the top metal layer composed of a periodic arrangement of arbitrary structural units, has the primary advantage of a simple structure. The periodicity of the top metal structure can be determined based on the position of the surface lattice resonance peak, enabling high-quality factor and high-sensitivity biochemical sensing. Based on actual needs, the lattice period, the thickness of the bottom and top metal layers, the thickness of the intermediate dielectric layer, and the top metal structure are optimized. By varying the lattice period and adjusting the position of the surface lattice resonance peak, the terahertz fingerprint spectra of different biochemical molecules are coupled, enabling precise detection of biochemical substances.

[0044] Although the embodiments of the present invention have been described, they are not limited to those shown in the specification and embodiments, and can be applied to various fields suitable for the present invention. It will be understood by those skilled in the art that various changes and improvements can be made to the embodiments without departing from the principles and purpose of the present invention, and all of these fall within the scope of protection of the present invention. The scope of the present invention is defined by the claims and their equivalents.

Claims

1. A method for detecting terahertz fingerprints of biochemical molecules, characterized in that: 1) preparing a terahertz metasurface sensor having a three-layer structure, wherein the bottom layer is a metal layer, the middle layer is a dielectric layer, and the top layer is a planar array of periodically arranged metal structures, wherein the periodic dimensions of the metal structures in the x-direction and the y-direction are the same; 2) Utilizing artificial surface plasmons and the metal structure in the top layer to generate Rayleigh anomalous diffraction coupling, the terahertz metasurface sensor forms a surface lattice resonance mode; 3) According to formula (1), calculate the surface lattice resonance peak f of the terahertz metasurface sensor SLRs : where c is the speed of light in a vacuum, n eff is the effective refractive index of the interface between the middle dielectric layer and the top metal layer, θ is the angle between the incident terahertz wave vector k and the z axis, m and n are integers of the diffraction order in the x and y directions, and P is the periodic size of the metal structure in the x and y directions; 4) Using the position of the surface lattice resonance peak of the terahertz metasurface sensor obtained in step 3) to couple the terahertz fingerprint spectra of different biochemical molecules, thereby realizing the detection of the terahertz fingerprint spectra of the biochemical molecules.

2. The method for detecting terahertz fingerprints of biochemical molecules according to claim 1, wherein: The bottom layer is made of gold, silver or copper, and has a thickness of H1, where H1 is ≥ 0.04 μm.

3. The method for detecting terahertz fingerprints of biochemical molecules according to claim 1, wherein: The intermediate layer is made of silicon dioxide, polytetrafluoroethylene or polyimide, and has a thickness of H2, 0.8 μm≤H2≤1.50 μm.

4. The method for detecting terahertz fingerprints of biochemical molecules according to claim 1, wherein: The metal structure in the top layer is made of gold, silver or copper, and has a thickness of H3, where H3 is ≥ 2.0 μm.

5. The method for detecting terahertz fingerprints of biochemical molecules according to claim 1, wherein: The shape of the metal structure is a rectangle, an open ring, a cross or a double rectangle.

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