Method for enhancing biological sample signal under terahertz near-field detection based on microstructure chip

Abstract

The invention discloses a method for enhancing a biological sample signal under terahertz near-field detection based on a microstructure chip. The method is based on an electromagnetic field theory, and the principle of enhancing terahertz near-field signals by the microstructure chip is disclosed by analyzing spatial distribution of a surface electric field of the microstructure chip under the action of a near-field probe. Research finds that the relative position between the probe and the microstructure chip has differentiated influence on the near-field intensity, and the optimal position of the sample can be determined by calculating the near-field intensity of the probe at different relative positions. Specifically, by changing the relative position of the probe and the microstructure and simulating to obtain the near-field intensity of the corresponding position, it is found that when the probe is located at the edge of the opening of the superstructure, the enhancement effect of the near-field signal is most significant. Compared with a traditional enhanced terahertz near-field biological sample detection method, the micro-structure chip is adopted as the substrate, and when the sample is placed at the edge of the opening of the micro-structure chip, the near-field signal of the biological sample can be enhanced by 4-5 times. According to the method, the detection sensitivity of the biological sample to be detected can be improved, the application range is wider, the cost is lower, and the method can adapt to different forms and types of biomedical samples.

Description

Technical Field

[0001] The present invention relates to a biological detection technology, and in particular to a method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip. Background Art

[0002] Terahertz detection technology (0.1-10.0 THz) has significant advantages in the field of biological detection, mainly because its single photon energy is low, which will not cause photoionization damage to biological samples. At the same time, it is highly sensitive to the structural characteristics of biological molecules such as vibration and rotation, and can provide characteristic spectra at the molecular level, thereby accurately analyzing the structure and conformation of biological molecules. Terahertz scattering scanning near-field optical microscopy technology can achieve sub-micron resolution, detect the structure and properties of biological samples that cannot be observed by traditional optical microscopes, break through the diffraction limit of traditional far-field microscopes, and achieve nanometer-level imaging and spectroscopy capabilities.

[0003] When terahertz scattering scanning near-field optical microscopy (s-SNOM) detects biological samples, the resulting scattered near-field signal is weak because the dielectric constant of biological samples is often small, resulting in the technology's lack of sensitivity in identifying components in biological samples and low resolution accuracy. This, to a certain extent, limits the development of terahertz near-field technology in the field of biomedical testing.

[0004] Therefore, there is an urgent need in the market for a biological sample detection method with high sensitivity and high resolution accuracy. Summary of the invention

[0005] Purpose of the invention: To address the problems of lack of sensitivity in identifying key components in samples and low resolution accuracy in traditional terahertz scattering scanning near-field optical microscopy, a terahertz near-field biological detection method based on microstructure chip enhanced sample signal is proposed, which can obtain stronger near-field signals and higher contrast near-field images.

[0006] Technical solution: A method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip, specifically comprising the following steps:

[0007] Step S1: designing a microstructure chip, wherein the microstructure chip comprises a substrate (1) and a microstructure (2);

[0008] Step S2: Based on the point dipole theory, a microstructure near-field model is constructed and the angle between the incident terahertz wave and the probe (3) is optimized to analyze the spatial distribution of the electric field on the surface of the microstructure chip under the action of the near-field probe (3) and clarify the principle of the microstructure chip enhancing the terahertz near-field signal;

[0009] Step S3: The electric field distribution on the surface of the microstructure chip is uneven, so the near-field signal enhancement effect will vary. In order to achieve the best near-field signal enhancement, the relative position of the probe (3) and the microstructure is adjusted and simulation is performed. The results show that when the probe (3) is placed at the position (4) of the microstructure chip, the most significant near-field signal enhancement effect can be obtained;

[0010] Step S4: placing the biological sample at position (4) of the microstructure chip and testing it using a terahertz near-field system to obtain enhanced near-field images and spectra for analyzing the composition and spatial distribution of the biological sample.

[0011] Furthermore, in the method of step S1, the material of the substrate (1) includes a material with high transmittance to terahertz waves, such as quartz glass, high-resistance silicon, borosilicate glass, etc.

[0012] Furthermore, in the method of step S1, the structure of the microstructure chip includes various asymmetric structures such as a "C"-shaped ring structure, a stick-shaped structure, a triangle structure, and a planar square ring structure.

[0013] Furthermore, in the method of step S1, the material of the microstructure of the microstructure chip includes gold, silicon, graphene, silicon dioxide, silicon nitride and other materials with high transparency to terahertz waves.

[0014] Furthermore, the method of step S1: the design and use of the microstructure chip include various methods such as reflection and transmission.

[0015] Furthermore, in the method of step S2, the angle between the incident terahertz wave and the probe (3) includes a plurality of angles such as 30°, 45°, and 60°.

[0016] Furthermore, in the method of step S3, the best position on the microstructure chip where electric field enhancement occurs is the position (4) of the microstructure.

[0017] Furthermore, the method of step S3: using an extremely sharp probe (3). The size of the probe (3) includes but is not limited to 1-10 nm, and the material used for the probe (3) includes platinum, gold and the like.

[0018] Furthermore, in the method of step S4, the sample includes proteins, cells, bacteria, etc.

[0019] Furthermore, the method of step S4: by using a microstructure chip, a substantial enhancement of the terahertz near-field intensity at the opening of the microstructure chip is achieved, so that after deducting the substrate (1) signal, the signal intensity of the biological sample is significantly improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be described in detail below in conjunction with the accompanying drawings, wherein:

[0021] Figure 1 Schematic diagram of the chip structure;

[0022] Figure 2 is the chip structure parameter;

[0023] Figure 3 This is the terahertz spectrum calculated by COMSOL;

[0024] Figure 4 is the incident light angle θ Impact on signal amplification effect;

[0025] Figure 5 This is the Ez electric field distribution diagram of the microstructure at 1.28 THz;

[0026] Figure 6 The Ez electric field distribution diagram of the microstructure chip when the probe (3) is located at the microstructure position (4) under the s-SNOM system;

[0027] Figure 7 is the scattered electric field distribution when the probe (3) is located at the microstructure position (4) in the s-SNOM system;

[0028] Figure 8 1 is the Ez electric field distribution diagram of the microstructure chip when the probe (3) is located at the position (5) of the microstructure chip under the s-SNOM system;

[0029] Fig. 9 : The scattered electric field distribution when the probe (3) is located at the position (5) of the microstructure chip in the s-SNOM system;

[0030] Fig.10 A schematic diagram of using a microstructure chip as a detection substrate;

[0031] Fig.11 A comparison chart of signal amplification using gold, silicon, and microstructure chips as substrates. DETAILED DESCRIPTION

[0032] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0033] The method of enhancing biological sample signals under terahertz near-field detection based on a microstructure chip in this embodiment includes the following specific steps:

[0034] (1) A reflective microstructure chip was designed using COMSOL simulation. Figure 1 It is a schematic diagram of the structure of the microstructure chip. Its unit structure parameters are as follows Figure 2 As shown in the figure, the chip substrate is 0.5 mm thick silicon, and the shaded part is coated with a 100 nm gold film. D1 is 17.8 μm, D2 is 11.4 μm, g is 3 μm, and p is 60 μm. The terahertz spectrum of the chip is shown in Figure 3 As shown, the resonance peak center frequency of the microstructure is at 1.28 THz.

[0035] (2) Based on the electric dipole theory, COMSOL was used to simulate the near-field model containing the microstructure chip. The probe (3) is composed of a cone and a hemisphere, where the top radius of the cone is 10 μm, the bottom radius is 20 nm, and the length is 80 μm. A hemisphere with a radius of 20 nm is added to the bottom of the cone to simulate the probe tip. The microstructure chip is located below the probe (3), and its geometric center is aligned with the probe vertex. The incident light is set as follows: the background field is defined as a linearly polarized plane wave, the electric field strength is E0 (the default is 1 V / M), and the wave vector direction is defined as parallel to the xz plane and the angle with the xy plane is θ , this setting ensures that the incident light source is a P-polarized plane wave. The external boundary of the model can be set to a perfectly matched layer. θ The value has an enhanced effect on the near-field signal. Figure 4 As shown, in this case, θ The best effect is at 40 degrees. θ values ​​for subsequent analysis.

[0036] (3) The Ez electric field distribution of the microstructure chip at 1.28 THz is as follows: Figure 5 As shown in the figure, the Ez electric field is concentrated at the edge of the ring-shaped opening. The electric field distribution on the surface of the microstructure chip is uneven, so the near-field signal enhancement effect will vary. By adjusting the relative position of the probe (3) and the microstructure and performing simulation, when the probe (3) is located as shown in the figure, the near-field signal enhancement effect will vary. Figure 6 The microstructure chip position (4) shown in the figure, the probe (3) interacts with the microstructure chip, the microstructure resonates strongly, and generates strong scattered light, such as Figure 7 When the probe (3) is located at Figure 8 When the microstructure chip is at position (5) as shown, the probe (3) interacts with the microstructure chip, and the microstructure resonates weakly, generating weak scattered light, such as Fig. 9 As shown in the figure, the location of the scattered light enhancement will also change for different microstructure chips, which requires specific calculation and analysis.

[0037] (4) Use terahertz near-field optical microscopy to obtain near-field images and spectra of biological samples, and analyze the composition and spatial distribution of biological samples: Fig.10 It is a schematic diagram of detection using a microstructure chip as a substrate in an s-SNOM system, wherein the probe (3) is located above the microstructure chip position (4). Fig.11 This is a signal amplification comparison chart using gold, silicon, and microstructure chips as substrates. As shown in the figure, compared with traditional gold and silicon substrates, the near-field signal using microstructure chips as substrates is enhanced by 4 to 5 times, which is more conducive to terahertz material identification of biomedical samples at the nanoscale.

[0038] The above is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any technician in the relevant technical field, without departing from the scope of the technical solution of the present invention, makes any form of equivalent replacement or modification to the technical solution and technical content disclosed in the present invention, which does not depart from the content of the technical solution of the present invention and still falls within the protection scope of the present invention.

Claims

1. A method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip, characterized in that: The specific steps include: Step S1: designing a microstructure chip, wherein the microstructure chip comprises a substrate (1) and a microstructure (2); Step S2: Based on the point dipole theory, a microstructure near-field model is constructed and the angle between the incident terahertz wave and the probe (3) is optimized to analyze the spatial distribution of the electric field on the surface of the microstructure chip under the action of the near-field probe (3) and clarify the principle of the microstructure chip enhancing the terahertz near-field signal; Step S3: The electric field distribution on the surface of the microstructure chip is uneven, so the near-field signal enhancement effect will vary. In order to achieve the best near-field signal enhancement, the relative position of the probe (3) and the microstructure is adjusted and simulation is performed. The results show that when the probe (3) is placed at the position (4) of the microstructure chip, the most significant near-field signal enhancement effect can be obtained; Step S4: placing the biological sample at position (4) of the microstructure chip and testing it using a terahertz near-field system to obtain enhanced near-field images and spectra for analyzing the composition and spatial distribution of the biological sample.

2. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S1: the material of the substrate (1) includes quartz glass, high-resistance silicon, borosilicate glass and other materials with high transmittance to terahertz waves.

3. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S1: The structure of the microstructure chip includes various asymmetric structures such as a "C"-shaped ring structure, a stick-shaped structure, a triangle structure, a planar square ring structure, etc.

4. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S1: the material of the microstructure chip microstructure includes gold, silicon, graphene, silicon dioxide, silicon nitride and other materials with high transparency to terahertz waves.

5. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S1: The design and use of the microstructure chip include various methods such as reflection type and transmission type.

6. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S2: the angle between the incident terahertz wave and the probe (3) includes a plurality of angles such as 30°, 45°, and 60°.

7. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S3: the best position for electric field enhancement on the microstructure chip is the position (4) of the microstructure.

8. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S3: using an extremely sharp probe (3). The size of the probe (3) includes but is not limited to 1-10 nm, and the material used for the probe (3) includes platinum, gold and other materials.

9. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S4: the sample includes proteins, cells, bacteria, etc.

10. The method for enhancing biological sample signals under terahertz near-field detection based on a microstructure chip according to claim 1, characterized in that: The method of step S4: by using a microstructure chip, a substantial enhancement of the terahertz near-field intensity at the opening of the microstructure chip is achieved, so that after deducting the substrate (1) signal, the signal intensity of the biological sample is significantly improved.

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