A terahertz all-dielectric biosensor with coupled bright and dark modes and its preparation method

Abstract

The present application relates to the technical field of terahertz metamaterial biosensors, and specifically to a terahertz all-dielectric biosensor with light and dark mode coupling and a preparation method. The present invention obtains an all-dielectric metamaterial biosensor by anodic bonding-photolithography patterning-etching-specific antibody modification. The sensor includes a dielectric layer and a substrate layer. The dielectric layer is composed of an array of open ring structures and rod-like structures of the all-dielectric metamaterial alternately. The two ends of the open ring structure are symmetrically open, and the opening connection line is parallel to the rod-like structure. The distances between the rod-like structure and the open ring structures on the left and right sides are u and v, respectively, and 5μm≥|v‑u|≥1μm. In the dielectric layer of the sensor of the present invention, the rod-like structure is used as the bright mode and the open ring structure is used as the dark mode. The two sets of arrays interact with each other to achieve light and dark mode coupling, split the resonance peak, increase the Q factor and sensitivity, so that the sensor has high sensitivity and low detection limit for low-concentration biological sample detection in the terahertz band, and the method is stable and reliable.

Description

Technical Field

[0001] The present invention relates to the technical field of terahertz metamaterial biosensors, and in particular to a terahertz all-dielectric biosensor with light and dark mode coupling and a preparation method thereof. Background Art

[0002] Electromagnetic metamaterials are sensitive to the surrounding dielectric environment and can enhance the electromagnetic field locally, so they have a wide range of application potential in the field of sensing. The working principle of biosensors based on electromagnetic metamaterials is to convert the change of the dielectric constant around the sensor into the change of the frequency domain spectrum of the electromagnetic signal, which is specifically manifested as the shift of the resonance peak position. The dielectric constant of the object to be tested is calculated by the shift of the resonance peak, and then the concentration of the sample to be tested is calculated. Since metamaterials have the effect of enhancing the electromagnetic field, the detection sensitivity of sensors using metamaterials is greatly improved.

[0003] Terahertz (THz) electromagnetic waves refer to electromagnetic waves with a frequency of 0.1-1THz, which have the characteristics of low energy (the energy of photons with a frequency of 1THz is about 4meV) and will not cause ionization damage and changes in biological tissues. Therefore, terahertz metamaterial biosensors have the characteristics of high sensitivity, low detection limit, label-free, non-destructive detection, etc., and have broad application prospects in the detection of extremely low concentration biological samples (such as tumor markers, cytokines, etc.). Among them, sensitivity, biocompatibility, pretreatment complexity, reliability, etc. are the main indicators for measuring the performance of biosensors, and the device Q factor (quality factor) is one of the important performance indicators of biosensors. The larger the Q factor, the sharper the resonance peak of the device's frequency domain transmission spectrum and the higher the sensitivity.

[0004] Metal-based metamaterials are the most widely studied metamaterial system. However, due to the thermal effect of electric current in metal materials, metal-based metamaterials have large losses and low Q factors, which limits the sensitivity of metal-based metamaterial biosensors. In order to obtain high-Q factor devices, all-dielectric metamaterials are increasingly valued and are increasingly widely used in the field of biosensing.

[0005] In addition, Fano resonance is a classic resonance mode, which can be simply understood as: it is generated by the interference of a discrete quantum state and a continuous state, and shows an obvious asymmetric peak in the excitation spectrum. Using Fano resonance to introduce an asymmetric peak is an effective means to improve the Q factor of the device. For example, Chinese patent CN107703101B discloses a biosensor based on a one-dimensional photonic crystal coupled micro-ring cavity, which introduces Fano resonance by etching a one-dimensional photonic crystal on the input straight waveguide, and the one-dimensional photonic crystal group includes a non-uniform circular hole group and a uniform circular hole group. Compared with the symmetrical line shape (Lorentz line shape) generated by the traditional micro-ring resonant cavity, the asymmetric line shape generated by Fano resonance is more advantageous in the field of sensing, but the biosensor of this patent is suitable for visible light and near-infrared light bands with longer wavelengths. At present, there are few studies on high Q factor biosensors used in the terahertz band. Summary of the invention

[0006] In order to solve the problems existing in the prior art and further improve the sensitivity of the all-dielectric metamaterial biosensor working in the terahertz band, the present invention proposes a terahertz all-dielectric biosensor with light and dark mode coupling and a preparation method. The specific scheme is as follows:

[0007] A terahertz all-dielectric biosensor with light and dark mode coupling includes a dielectric layer and a substrate layer. The dielectric layer is composed of two structures of all-dielectric metamaterials in the lateral direction, which are an open ring structure and a rod-shaped structure. The dielectric layer is composed of multiple open ring structures or multiple rod-shaped structures in the vertical direction. The two ends of the open ring structure are symmetrically open, and the connecting line of the two openings is parallel to the rod-shaped structure. The distances between the rod-shaped structure and the open ring structures on the left and right sides are u and v, respectively, u=15-30 μm, v=15-30 μm, and 5 μm≥|vu|≥1μm. The rod-shaped structure is a light mode, and the open ring structure is a dark mode.

[0008] Furthermore, the two left and right open ring structures and the rod-shaped structure form a unit structure, the period length P of each unit structure in the lateral direction is 200-290 μm, the width a of the rod-shaped structure is 40-60 μm, the length b of the rod-shaped structure is 195-280 μm, the outer radius R of the open ring structure is 70-80 μm, the inner radius r of the open ring structure is 0-60 μm, and the opening width g of the open ring structure is 4-10 μm.

[0009] Furthermore, the all-dielectric metamaterial of the dielectric layer is a high-resistance silicon single crystal, with a resistivity of more than 5000Ω·cm and a thickness of 100-600μm.

[0010] Furthermore, the substrate layer is silicate glass, and specific glass materials include Schott BF33, Schott BK7 glass, and Corning 7070 glass, with a real part of the dielectric constant ε<3 in the 0.1-1 THz frequency band and a thickness of 200-500 μm.

[0011] The method for preparing the above-mentioned bright and dark mode coupled terahertz all-medium biosensor comprises the following steps:

[0012] Step 1: Anodically bonding the unpatterned dielectric layer to the substrate layer. Preferably, the bonding process parameters include a temperature of 300-400° C., a voltage of 800-1000 V, and a bonding time of 20-30 min.

[0013] Step 2: Then, glue is applied on the surface of the dielectric layer, and the surface is exposed and patterned by photolithography to obtain a rod-open ring device pattern;

[0014] Step 3: Etching the dielectric layer again until the substrate layer is cut off, thereby obtaining a dielectric layer composed of an open ring structure and a rod-shaped structure;

[0015] Step 4: The surface of the whole device is modified with specific antibodies to obtain a biosensor.

[0016] Furthermore, in step 4, H is first used 2 SO 4 and H 2 O 2 The entire device surface is cleaned with a mixed solution, the surface of the dielectric layer is then cleaned with oxygen plasma, and the device is then immersed in a 3-aminopropyltriethoxysilane solution, and then immersed in a mixed solution of carbodiimide solution, N-hydroxysulfosuccinimide and the corresponding antibody of the biological sample to be tested to perform amino modification on the sensor surface.

[0017] Furthermore, the H 2 SO 4 and H 2 O 2 The volume ratio is 4:1.

[0018] Furthermore, during the oxygen plasma cleaning process, the oxygen plasma power is 30-80 W, and the bombardment time is 2-8 min.

[0019] Further, a 3-aminopropyltriethoxysilane solution with a volume fraction of 1%-10% is used for immersion at 60-90° C. for 1-4 hours.

[0020] Furthermore, the temperature of the mixed solution of the carbodiimide solution, N-hydroxysulfosuccinimide and the antibody corresponding to the biological sample to be tested is maintained at 35-39° C., and the immersion time is 1-24 hours.

[0021] Broadband "bright" mode resonant units (accessible from free space) and narrowband "dark" mode resonant units (a very small number of which can enter from free space or cannot enter) will interfere with each other under the condition that the space and frequency domains are very close, forming an extremely narrow reflection or transmission window. Due to the low radiation loss of the dark mode, the Fano resonance can be very sharp, resulting in a very narrow bandwidth, i.e., a high Q factor, for the sample. In the present invention, the "bright" mode adopts a rod-shaped structure. The rod-shaped structure is the shape that is most prone to electric dipole resonance and can be regarded as an electric dipole resonant antenna. A structure that does not resonate simultaneously with the rod-shaped structure in the same direction of the incident electric field can be used as a "dark" mode structure, but a "dark" mode is required in other directions to form a dipole resonance. Therefore, the present invention designs an open ring structure as a "dark" mode. The open ring structure has obvious advantages over a ring structure or a circular structure because it has a significant electromagnetic field enhancement effect at its open ring slit. Further, by adjusting the spacing between the bright and dark modes, the bright and dark mode coupling is achieved to form a Fano resonance and generate a resonance splitting peak. The structural schematic diagram is shown in the attached figure. Figure 1 , 2 The simulated electromagnetic field distribution diagram is shown in the attached Figure 3 shown.

[0022] Fano resonance can be analyzed by using a spring oscillator model, as shown in the attached figure. Figure 4 As shown in the figure: There are two interconnected spring oscillators in the model, of which oscillator 1 is directly affected by external forces (bright mode), while oscillator 2 is not directly affected by external forces but can be driven to vibrate by oscillator 1 (dark mode). A simple harmonic external force with an angular frequency of ω is applied to the system, and the two oscillators in the system can be expressed as:

[0023]

[0024] in, , represents the resonance strength of the two resonance units, , Represents the resonant angular frequency of a single resonant unit, , represents the damping coefficient, represents the system resonant frequency, , Represents the driving force of resonance, and α represents the coupling coefficient between the two resonant units. In the structure of the present invention, the rod-shaped structure in a unit structure is a bright mode, that is, it can be directly excited, which is equivalent to the oscillator 1 in the model, and the open ring structure is a dark mode, which is equivalent to the oscillator 2 in the model, and cannot be directly excited, but is excited by the influence of oscillator 1. Adjusting the spacing between the two structures of the rod and the open ring, that is, adjusting the mutual coupling between the two oscillators, that is, adjusting the coupling coefficient α. Therefore, the relationship between the spacing v and u between the two structures of the rod and the open ring is an important parameter for regulating the coupling of bright and dark modes, which directly affects the size of the device Q factor: if v=u, it is a completely symmetrical structure, and no coupling effect of bright and dark modes will be produced, no splitting peak will appear, and a large Q factor device cannot be obtained. In order to obtain the best light and dark mode coupling effect, the v and u values ​​are calculated and analyzed. When the relationship between v and u satisfies 5 μm≥|vu|≥1 μm, the device has a larger Q factor. The difference between v and u corresponds to the spring elastic coefficient (i.e., coupling coefficient) α of the connecting part of the two oscillators in the Fano resonant spring oscillator model.

[0025] The beneficial effects of the present invention are:

[0026] (1) The upper dielectric layer of the biosensor of the present invention is made of high-resistance silicon, and the lower substrate layer is made of glass. The two form a dielectric constant difference, so that the electromagnetic wave can propagate in the upper dielectric layer as much as possible. Since the resistivity of high-resistance silicon is large, a displacement current is formed inside, there is almost no thermal effect, and the energy loss is low. Compared with metal-based metamaterials, it has a larger Q factor;

[0027] (2) In the design of the high-resistance silicon dielectric layer structure, the open ring structure is used as the dark mode. There is an obvious electric field enhancement effect at the slit of the open ring, which can improve the detection sensitivity of the sensor and has a better effect than other non-open ring structures. At the same time, the unit structure composed of the open ring structure and the rod-shaped structure is alternately arranged in an array, the rod-shaped structure is the bright mode, and the open ring structure is the dark mode, so as to realize the coupling of the bright and dark modes, introduce Fano resonance, generate a resonant splitting peak, and further adjust the spacing between the bright and dark modes to make the device have a larger Q factor, so that it has a lower detection limit and higher sensitivity in the terahertz band;

[0028] (3) The bonding-photolithography-etching process adopted by the present invention facilitates large-scale production of devices, improves device reliability and reduces costs. The silicon-glass bonding process is adopted, and the upper dielectric layer is a high-resistance silicon single crystal. The intrinsic electromagnetic parameters such as the dielectric constant are stable and unchanged. Compared with the silicon film obtained by sputtering deposition, the electromagnetic parameters are relatively stable, and the resistivity fluctuation is small. The technical route of the present invention is more convenient and reliable for device design. In addition, the high-resistance silicon material has good biocompatibility, and it is easy to form silane bonds during the modification process, and it is easy to combine with antibodies, which enhances the selectivity of the biosensor. The preparation route of the present invention finally performs amino modification on the surface of the biosensor, which further improves the biocompatibility and selectivity of the biosensor.

[0029] The present invention realizes light and dark mode coupling by constructing an alternating arrangement of unit structures composed of an open ring structure and a rod-shaped structure, introduces Fano resonance, and improves its Q factor in the terahertz band, so that the biosensor of the present invention can be used for the detection of biological samples including proteins, nucleic acids, peptides, cytokines, etc., has a lower detection limit and higher sensitivity, and will not cause ionization damage and changes to biological tissues. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The embodiments of the present invention are further described below with reference to the accompanying drawings, in which:

[0031] Figure 1 A schematic diagram of the structure of the biosensor of the present invention (left) and a scanning electron microscope image of the dielectric layer (right) are shown;

[0032] Figure 2 A schematic top view of a unit structure in a medium layer of a biosensor of the present invention is shown;

[0033] Figure 3 The simulated electromagnetic field distribution diagram of a unit structure in the medium layer of the biosensor of the present invention is shown, a is a schematic diagram of the cross-sectional position of the device, the heights from the bonding surface are Ⅰ: 50μm, Ⅱ: 100μm, Ⅲ: 150μm, b, c, d are the electric field distribution diagrams at the three cross sections Ⅰ, Ⅱ, Ⅲ in a respectively;

[0034] Figure 4 A spring oscillator model is shown;

[0035] Figure 5 The THz transmission spectrum (left) and sensitivity fitting curve (right) of Example 1 of the present invention are shown;

[0036] Figure 6 The THz transmission spectrum (left) and sensitivity fitting curve (right) of Example 2 of the present invention are shown;

[0037] Figure 7The THz transmission spectrum (left) and sensitivity fitting curve (right) of Comparative Example 1 of the present invention are shown;

[0038] Figure 8 A schematic top view of a unit structure in a biosensor medium layer of Comparative Example 2 is shown;

[0039] Fig. 9 The THz transmission spectrum (left) and the sensitivity fitting curve (right) of Comparative Example 2 of the present invention are shown. DETAILED DESCRIPTION

[0040] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below through specific embodiments in conjunction with the accompanying drawings. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. Example 1

[0041] The dielectric layer is high-resistance silicon. The lateral direction of the dielectric layer is composed of alternating open ring structures and rod-shaped structures of high-resistance silicon. The vertical direction of the dielectric layer is composed of multiple alternating open ring structures or multiple alternating rod-shaped structures. The two ends of the open ring structure are symmetrically open, and the two opening lines are parallel to the rod-shaped structure. The distances between the rod-shaped structure and the open ring structures on the left and right sides are u and v, v=27 μm, u=24 μm, satisfying |vu|=3 μm; the other parameters of the device structure are as follows: the width of the rod-shaped structure a =50 μm; the length of the rod-shaped structure b=240 μm; the opening width of the open ring structure g =8 μm, the outer radius of the open ring structure R =75 μm; the inner radius of the open ring structure r=37 μm; the left and right open ring structures and the rod-shaped structure are a unit structure, and the period length of each unit structure in the lateral direction P =251 μm. The substrate layer is Schott BF33 glass, the resistivity of high-resistance silicon is 8000Ω·cm, and the thickness h 1 200 μm; the thickness of the bottom glass material h 2 The thickness of the material is 300 μm, and the real part of the dielectric constant ε=2.14 in the 0.1-1 THz frequency band. The metamaterial biosensor with light and dark mode coupling was obtained by anodic bonding, photolithography patterning, etching, and surface modification. The specific preparation process is as follows: the high-resistance silicon (dielectric layer) to be bonded is connected to the positive electrode of the power supply, and the BF33 glass (substrate layer) is connected to the negative electrode. The glass-silicon wafer is heated to 350°C at a voltage of 1000V, bonded for 30 minutes, and the high-resistance silicon is bonded to the BF33 glass; the upper layer of the open ring structure and the rod-shaped structure is covered with positive photoresist, and the above-mentioned size pattern is obtained by photolithography; the upper layer of high-resistance silicon is etched to a depth of 200 μm, and the bonding interface is cut off; a volume ratio of 4:1 H 2 SO 4 and H 2 O 2The surface of the whole device is cleaned with a mixed solution of , and then the surface of the dielectric layer is cleaned with oxygen plasma. The oxygen plasma power is 50W and the bombardment time is 6min. The upper photoresist is removed to increase the roughness of the device and make its surface easy to bind with antibodies. After cleaning, the device is immersed in a 5% volume fraction 3-aminopropyltriethoxysilane solution at 80℃ for 3h, and then immersed in a 35℃ carbodiimide solution, N-hydroxysulfosuccinimide and a mixed solution of the corresponding antibody of the biological sample to be tested for 10h for specific antibody modification to obtain a biosensor. Among them, the horizontal and vertical expressions are relative positions.

[0042] The device was applied to the detection of cytokine interleukin 6 (IL-6). Six different concentrations of IL-6 biological sample solutions were prepared with bovine serum as solvent: 100 pg / mL, 1 ng / mL, 10 ng / mL, 100 ng / mL, 1 μg / mL, and 10 μg / mL. The THz transmission spectra and sensitivity equation fitting results are shown in the attached figure. Figure 5 shown.

[0043] In the range of 100 pg / mL to 10 μg / mL, the high-frequency resonance peak frequency shift ∆f is roughly linear with the logarithm of the concentration. The resonance peak position f and the concentration c are fitted to obtain equation (1). The absolute value of the slope of the equation represents the sensitivity. The larger the absolute value of the slope, the higher the sensitivity. The sensitivity of the device is 0.00209. The resonance peak Q factor is calculated using the formula Q=f / FWHM, where f is the resonance peak frequency and FWHM is the half-width of the resonance peak. The resonance peak Q factor is about 55.

[0044] f=-0.00209×lg(c)+0.58458 (1) Example 2

[0045] The dielectric layer is high-resistance silicon. The lateral direction of the dielectric layer is composed of alternating open ring structures and rod-like structures of high-resistance silicon. The vertical direction of the dielectric layer is composed of multiple alternating open ring structures or multiple alternating rod-like structures. The two ends of the open ring structure are symmetrically open, and the two opening lines are parallel to the rod-like structure. The distances between the rod-like structure and the open ring structures on the left and right sides are u and v, v=28 μm, u=26 μm, satisfying |vu|=2 μm; the other parameters of the device structure are specifically the width of the rod-like structure a=45 μm; the length of the rod-like structure b=220 μm; the opening width of the open ring structure g=9 μm, the outer radius of the open ring structure R=78 μm; the inner radius of the open ring structure r=20 μm; the left and right open ring structures and the rod-like structure are a unit structure, and the period length of each unit structure in the lateral direction P=255 μm. The substrate layer is Schott BF33 glass, the resistivity of high-resistance silicon is 9000Ω·cm, and the thickness h 1200 μm; the thickness of the bottom glass material h 2 The thickness is 300 μm, and in the frequency range of 0.1-1 THz, the real part of the dielectric constant ε=2.14. The preparation method is the same as that in Example 1. Wherein, the horizontal and vertical directions are relative positions.

[0046] The device was applied to the detection of carbohydrate antigen 125 (CA125). Six different concentrations of CA125 biological sample solutions were prepared with bovine serum as solvent: 100 pg / mL, 1 ng / mL, 10 ng / mL, 100 ng / mL, 1 μg / mL, and 10 μg / mL. The THz transmission spectra and sensitivity equation fitting results are shown in the attached figure. Figure 6 shown.

[0047] In the range of 100 pg / mL to 10 μg / mL, the high-frequency resonance peak frequency shift ∆f is roughly linear with the logarithm of the concentration. The resonance peak position f and the concentration c are fitted to obtain equation (2). The absolute value of the slope of the equation represents the sensitivity. The larger the absolute value of the slope, the higher the sensitivity. The sensitivity of the device is 0.00173. The resonance peak Q factor is calculated using the formula Q=f / FWHM, where f is the resonance peak frequency and FWHM is the half-width of the resonance peak. The resonance peak Q factor is about 48.

[0048] f=-0.00173×lg(c)+0.7525 (2)

[0049] Comparative Example 1

[0050] The dielectric layer is high-resistance silicon, the substrate layer is Schott BF33 glass, and the dielectric layer thickness is h 1 is 5 μm, and the thickness of the bottom glass material is h 2 The thickness of the upper layer of silicon is 300 μm, and the real part of the dielectric constant ε=2.14 in the frequency band of 0.1-1 THz. The upper layer of silicon is prepared by sputtering; the pattern is obtained by photolithography; the upper layer of high-resistance silicon is etched to a depth of 5 μm, and the etching depth is cut off at the bonding interface; the upper layer of photoresist is removed, and the specific process is the same as in Example 1. After cleaning, specific antibody modification is performed to obtain a metamaterial biosensor with light and dark mode coupling. The upper layer of dielectric silicon is obtained by sputtering deposition, photolithography patterning, etching, and surface modification to obtain a metamaterial biosensor with light and dark mode coupling. The graphic structure of the dielectric layer is the same as that in Example 1, and the device structure parameters are a=50 μm, b=240 μm, g=8 μm, R=75 μm, r=37 μm, P=251 μm, v=27 μm, u=24 μm, satisfying |vu|=3 μm.

[0051] The device was applied to the detection of cytokine interleukin 6 (IL-6). Five different concentrations of IL-6 biological sample solutions were prepared with bovine serum as solvent: 100 pg / mL, 1 ng / mL, 10 ng / mL, 100 ng / mL, and 1 μg / mL. The THz transmission spectrum and sensitivity equation fitting results are shown in Figure 2. Figure 7 shown.

[0052] In the range of 100 pg / mL to 1 μg / mL, the high-frequency resonance peak frequency shift ∆f is roughly linear with the logarithm of the concentration. The resonance peak position f and the concentration c are fitted to obtain equation (3). The absolute value of the slope represents the sensitivity, which is 0.00079. The resonance peak Q factor is calculated using the formula Q=f / FWHM, where f is the resonance peak frequency and FWHM is the half-width of the resonance peak. The resonance peak Q factor is about 32.

[0053] f=-0.00079×lg(c)+0.74612 (3)

[0054] It can be seen from Comparative Example 1 that the Q factor and sensitivity of the device prepared by the sputtering deposition method are significantly smaller than those of the device prepared by the bonding method, and the performance is poor.

[0055] Comparative Example 2

[0056] The dielectric layer is high-resistance silicon, the substrate layer is Schott BF33 glass, and the dielectric layer thickness is h 1 is 200 μm, the thickness of the bottom glass material h 2 The dielectric layer of this comparative example has a structure of a closed ring and a rod combination, as shown in the attached figure. Figure 8 shown.

[0057] The device structural parameters are a=45 μm, b=220 μm, R=78 μm, r=20 μm, P=255 μm, v=28 μm, u=26 μm, satisfying |vu|=2 μm.

[0058] The device was applied to the detection of carbohydrate antigen 125 (CA125). Six different concentrations of carbohydrate antigen 125 (CA125) biological sample solutions were prepared with bovine serum as solvent: 100 pg / mL, 1 ng / mL, 10 ng / mL, 100 ng / mL, 1 μg / mL, and 10 μg / mL. The THz transmission spectrum and sensitivity equation fitting results are shown in Figure 2. Fig. 9 shown.

[0059] In the range of 100 pg / mL to 1 μg / mL, the high-frequency resonance peak frequency shift ∆f is roughly linear with the logarithm of the concentration. The resonance peak position f and the concentration c are fitted to obtain equation (4). The absolute value of the slope represents the sensitivity, which is 0.00054. The resonance peak Q factor is calculated using the formula Q=f / FWHM, where f is the resonance peak frequency and FWHM is the half-width of the resonance peak. The resonance peak Q factor is about 20.

[0060] f=-0.00054×lg(c)+0.6507 (4)

[0061] It can be seen from Comparative Example 2 that the Q factor and sensitivity of the slitless circular ring structure as a dark mode device are significantly smaller than those of the open ring structure as a dark mode device, and the performance is poor.

[0062] Some exemplary embodiments of the present invention are described above. It can be understood that the above embodiments are only used to explain the present invention and do not constitute a limitation on the protection scope of the present invention. The features in these embodiments can be recombined in a suitable manner, and the scheme obtained thereby is still within the protection scope required by the present invention. Based on the above embodiments, all other embodiments obtained by those skilled in the art without making creative work, that is, all modifications, equivalent substitutions and improvements made within the spirit and principles of this application, fall within the protection scope required by the present invention.

Claims

1. A terahertz all-medium biosensor with light and dark mode coupling, comprising a dielectric layer and a substrate layer, characterized in that: The dielectric layer is composed of two structures of all-dielectric metamaterials in the lateral direction, which are an open ring structure and a rod-shaped structure. The dielectric layer is composed of multiple open ring structures or multiple rod-shaped structures in the vertical direction. The two ends of the open ring structure are symmetrically open, and the connecting line of the two openings is parallel to the rod-shaped structure. The distances between the rod structure and the open ring structures on the left and right sides are u and v, respectively, u=24-30μm, v=27-30μm, 5μm≥|vu|≥1μm; the two open ring structures on the left and right sides are The rod-like structure is a unit structure, the period length P of each unit structure in the lateral direction is 200-290μm, the width a of the rod-like structure is 40-60μm, the length b of the rod-like structure is 195-280μm, the outer radius R of the open ring structure is 70-80μm, the inner radius r of the open ring structure is 0-60μm, and the opening width g of the open ring structure is 4-10μm; the all-dielectric metamaterial of the dielectric layer is a high-resistance silicon single crystal with a resistivity of more than 5000Ω·cm and a thickness of 100-600μm.

2. The terahertz all-medium biosensor with light and dark mode coupling according to claim 1, characterized in that: The substrate layer is silicate glass, the real part of the dielectric constant ε in the 0.1-1THz frequency band is less than 3, and the thickness is 200-500μm.

3. The method for preparing the bright and dark mode coupled terahertz all-medium biosensor according to any one of claims 1 to 2, characterized in that: The following steps are involved: Step 1: Anodically bonding the unpatterned dielectric layer to the substrate layer; Step 2: Then, glue is applied on the surface of the dielectric layer, and the surface is exposed and patterned by photolithography to obtain a rod-open ring device pattern; Step 3: Etching the dielectric layer again until the substrate layer is cut off, thereby obtaining a dielectric layer composed of an open ring structure and a rod-shaped structure; Step 4: The surface of the whole device is modified with specific antibodies to obtain a biosensor.

4. The preparation method according to claim 3, characterized in that: In step 4, the entire device surface is first cleaned with a mixed solution of H2SO4 and H2O2, and then the surface of the dielectric layer is cleaned with oxygen plasma. The device is then immersed in a 3-aminopropyltriethoxysilane solution, and then immersed in a mixed solution of carbodiimide solution, N-hydroxysulfosuccinimide and the corresponding antibody of the biological sample to be tested to perform amino modification on the sensor surface.

5. The preparation method according to claim 4, characterized in that: The volume ratio of H2SO4 and H2O2 is 4:

1.

6. The preparation method according to claim 4, characterized in that: During the oxygen plasma cleaning process, the oxygen plasma power is 30-80 W and the bombardment time is 2-8 min.

7. The preparation method according to claim 4, characterized in that: Use 1%-10% volume fraction of 3-aminopropyltriethoxysilane solution and soak at 60-90℃ for 1-4 hours.

8. The preparation method according to claim 4, characterized in that: The temperature of the mixed solution of carbodiimide solution, N-hydroxysulfosuccinimide and the antibody corresponding to the biological sample to be tested is maintained at 35-39° C., and the immersion time is 1-24 hours.

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